Review
BibTex RIS Cite

Üremede Leptinlerin Etkisi

Year 2024, Volume: 9 Issue: 1, 98 - 114, 30.04.2024

Oya Korkmaz , Ömer Faruk Karaşör , Ali Soleimanzadeh , Mustafa Numan Bucak , Sadık Küçükgünay , Mustafa Kul

https://doi.org/10.51754/cusbed.1459267

Abstract

Adipoz doku hem enerji deposu hem de adipokinler olarak adlandırılan biyolojik olarak önemli çok sayıda molekülü salgılayan aktif bir endokrin organ olarak işlev görmektedir. Adipokinlerin üreme fonksiyonlarının düzenlenmesinde yer aldığı kanıtlanmıştır ve tanımlanan ilk adipokin leptindir. Son yıllarda yapılan araştırmalar, leptinin beyine giden enerji depolarının miktarının yalnızca yağ dokusundan türetilen bir habercisi olmadığını, aynı zamanda iltihaplanma, anjiyogenez, hematopoez, bağışıklık fonksiyonu ve üreme gibi bir dizi farklı fizyolojik süreç için çok önemli bir hormon/sitokin olduğunu göstermektedir. Adiposit kaynaklı bir hormon olan leptin, özellikle ergenlik ve üreme döneminde vücutta çok sayıda fizyolojik ve metabolik fonksiyonda önemli rol oynamaktadır. Leptin, merkezi hipotalamik etkilerinin yanı sıra, testisler de dahil olmak üzere birçok periferik organda (mide, iskelet kası, hipofiz hücreleri, plasenta) etki göstermektedir ve hem erkek üreme hem de dişi üreme işlevinde düzenleyici bir role sahiptir. Leptin normal üreme işlevi için gereklidir, ancak fazla miktarda bulunduğunda üreme sistemi üzerinde zararlı etkileri olabilir. Non-obstrüktif azoospermi, oligozoospermi ve oligo-asteno-teratozoospermi dahil olmak üzere testiküler parankimi etkileyen bozuklukları olan infertil erkeklerin yüksek leptin konsantrasyonlarına sahip olduğu bilinmektedir. Literatürde yapılan son çalışmalar, hipotalamik-hipofizeal-gonadal (HPG) ekseni, androjen regülasyonu ve sperm üretimi ile leptin ve infertilite arasında güçlü bir ilişki olduğunu öne sürmektedir. Yapılan bu çalışmalardan yola çıkarak, leptin fazlalığı, eksikliği veya direnci durumlarının anormal üreme işlevi ile ilişkili olabileceğini söylemek mümkündür. Ayrıca, yüksek leptinin neden olduğu bu anormallikler artan oksidatif stres ile de ilişkilendirilmiştir. Eğer ki leptin ve üreme arasındaki ilişki tam olarak anlaşılabilirse, hem erkek hem de kadın infertilitesi için gelecekte hedeflenen tedavilere ışık tutabilecektir. Bu derleme leptin ile fertilite arasındaki ilişkiye odaklanmaktadır.

Keywords

Üreme Hipotalamik-Hipofizeal-gonadal eksen İnfertilite Leptin

Ethical Statement

Bu çalışma için etik kurul onayı gerekli değildir.

Supporting Institution

Çalışma için herhangi bir finansal destek alınmamıştır.

References

  • Abbasihormozi, S., Shahverdi, A., Kouhkan, A., Cheraghi, J., Akhlaghi, A.A., & Kheimeh, A. (2013). Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat. Arch Gynecol Obstet, 287, 1241-9.
  • Abir, R., Ao, A., Jin, S., Barnett, M., Raanani, H., Ben-Haroush, A., & Fisch, B. (2005) Leptin and its receptors in human fetal and adult ovaries. Fertil Steril, 84, 1779-82.
  • Achache, H., & Revel, A. (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update, 12, 731-46.
  • Adam, C.L., Archer, Z.A., & Miller, D.W. (2003). Leptin actions on the reproductive neuroendocrine axis in sheep. Reprod Suppl, 61, 283-97.
  • Adam, C.L., Findlay, P.A., & Miller, D.W. (2006). Blood-brain leptin transport and appetite and reproductive neuroendocrine responses to intracerebroventricular leptin injection in sheep: influence of photoperiod. Endocrinology, 147, 4589-98.
  • Agarwal, A., Ikemoto, I., & Loughlin, K.R. (1994). Relationship of sperm parameters with levels of reactive oxygen species in semen specimens. J Urol, 152, 107-10.
  • Agarwal, A., Prabakaran, S.A., & Said, T.M. (2005). Prevention of oxidative stress injury to sperm. J Androl, 26, 654-60.
  • Agarwal, A., & Saleh, R.A. (2002). Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am, 29, 817-27.
  • Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab. 1999;84:1072-6.
  • Ahima, R.S., Dushay, J., Flier, S.N., Prabakaran, D., & Flier, J.S. (1997). Leptin accelerates the onset of puberty in normal female mice. J Clin Invest, 99, 391-5.
  • Ahima, R.S., & Flier, J.S. Leptin. (2000). Annu Rev Physiol, 62, 413-37.
  • Aiston, S., & Agius, L. (1999). Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin. Diabetes, 48, 15-20.
  • Aitken, R.J., Smith, T.B., Jobling, M.S., Baker, M.A., & De Iuliis, G.N. (2014). Oxidative stress and male reproductive health. Asian J Androl, 16, 31-8.
  • Almabhouh, F.A., Osman, K., Ibrahim, S.F., Gupalo, S., Gnanou, J., Ibrahim, E., & Singh, H.J. (2017). Melatonin ameliorates the adverse effects of leptin on sperm. Asian J Androl, 19, 647-654.
  • Almabhouh, F.A., Osman, K., Siti Fatimah, I., Sergey, G., Gnanou, J., & Singh, H.J. (2015). Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period. Andrologia, 47, 751-8.
  • Almabhouh, F.A., & Singh, H.J. (2023). The impact of leptin on sperm. Reprod Fertil Dev, 35(8), 459-468.
  • Almog, B., Gold, R., Tajima, K., Dantes, A., Salim, K., Rubinstein, M., Barkan, D., Homburg, R., Lessing, J.B., Nevo, N., Gertler, A., & Amsterdam, A. (2001). Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats. Mol Cell Endocrinol, 183, 179-91.
  • Amstalden, M., Garcia, M.R., Stanko, R.L., Nizielski, S.E., Morrison, C.D., Keisler, D.H., & Williams, G.L. (2002). Central infusion of recombinant ovine leptin normalizes plasma insulin and stimulates a novel hypersecretion of luteinizing hormone after short-term fasting in mature beef cows. Biol Reprod, 66, 1555-61.
  • Amstalden, M., Garcia, M.R., Williams, S.W., Stanko, R.L., Nizielski, S.E., Morrison, C.D., Keisler, D.H., & Williams, G.L. (2000). Leptin gene expression, circulating leptin, and luteinizing hormone pulsatility are acutely responsive to short-term fasting in prepubertal heifers: relationships to circulating insulin and insulin-like growth factor I(1). Biol Reprod, 63, 127-33.
  • Andrews, J.F. (1998). Leptin: energy regulation and beyond to a hormone with pan-physiological function. Proc Nutr Soc, 57, 409-11.
  • Angelopoulou, R., & Kyriazoglou, M. (2005). Sperm oxidative damage and the role of reactive oxygen species in male infertility. Arch Hell Med, 22,433-46.
  • Aquila, S., Gentile, M., Middea, E., Catalano, S., & Andò, S. (2005). Autocrine regulation of insulin secretion in human ejaculated spermatozoa. Endocrinology, 146, 552-7.
  • Aquila, S., Gentile, M., Middea, E., Catalano, S., Morelli, C., Pezzi, V., & Andò, S. (2005). Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab, 90, 4753-61.
  • Arias-Alvarez, M., Bermejo-Alvarez, P., Gutierrez-Adan, A., Rizos, D., Lorenzo, P.L., & Lonergan, P. (2011). Effect of leptin supplementation during in vitro oocyte maturation and embryo culture on bovine embryo development and gene expression patterns. Theriogenology, 75, 887-96.
  • Ashworth, C.J., Hoggard, N., Thomas, L., Mercer, J.G., Wallace, J.M., & Lea, R.G. (2000). Placental leptin. Rev Reprod, 5, 18-24.
  • Aziz, N., Saleh, R.A., Sharma, R.K., Lewis-Jones, I., Esfandiari, N., Thomas, A.J.Jr., & Agarwal, A. (2004). Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril, 81, 349-54.
  • Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J.P., Bortoluzzi, M.N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., & Lewin, M.J. (1998). The stomach is a source of leptin. Nature, 394, 790-3.
  • Barash, I.A., Cheung, C.C., Weigle, D.S., Ren, H., Kabigting, E.B., Kuijper, J.L., Clifton, D.K., & Steiner, R.A. (1996). Leptin is a metabolic signal to the reproductive system. Endocrinology, 137, 3144-7.
  • Barb, C.R., Barrett, J.B., Kraeling, R.R., & Rampacek, G.B. (1999). Role of leptin in modulating neuroendocrine function: a metabolic link between the brain-pituitary and adipose tissue. Reprod Domest Anim, 34, 111-26.
  • Batra, A., Okur, B., Glauben, R., Erben, U., Ihbe, J., Stroh, T., Fedke, I., Chang, H.D., Zeitz, M., & Siegmund, B. (2010). Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology, 151, 56-62.
  • Bellmann, O., Wegner, J., Teuscher, F., Schneider, F., & Ender, K. (2004). Growth differences and corresponding hormone concentrations in different metabolic type of cattle. Livestock Produc Sci, 85,45-57.
  • Bernabucci, U., Basiricò, L., Lacetera, N., Morera, P., Ronchi, B., Accorsi, P.A., Seren, E., & Nardone, A. (2006). Photoperiod affects gene expression of leptin and leptin receptors in adipose tissue from lactating dairy cows. J Dairy Sci, 89, 4678-86.
  • Bertoni, L., Ferretti, M., Cavani, F., Zavatti, M., Resca, E., Benelli, A., & Palumbo, C. (2009). Leptin increases growth of primary ossification centers in fetal mice. J Anat, 215, 577-83.
  • Bjørbaek, C., Uotani, S., Da Silva, B., & Flier, J.S. (1997). Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem, 272, 32686-95.
  • Blanca, A.J., Ruiz-Armenta, M.V., Zambrano, S., Salsoso, R., Miguel-Carrasco, J.L., Fortuño, A., Revilla, E., Mate, A., & Vázquez, C.M. (2016). Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine. J Cell Biochem, 117, 2281-8.
  • Boden, G., Chen, X., Mozzoli, M., & Ryan, I. (1996). Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab, 81, 3419-23.
  • Boelhauve, M., Sinowatz, F., Wolf, E., & Paula-Lopes, F.F. (2005). Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts. Biol Reprod, 73, 737-44.
  • Bouloumié, A., Drexler, H.C., Lafontan, M., & Busse, R. (1998). Leptin, the product of Ob gene, promotes angiogenesis. Circ Res, 83, 1059-66.
  • Brandão, C.M., Lombardi, M.T., Nishida, S.K., Hauache, O.M., & Vieira, J.G. (2003). Serum leptin concentration during puberty in healthy nonobese adolescents. Braz J Med Biol Res, 36, 1293-6.
  • Brannian, J.D., Zhao, Y., & McElroy, M. (1999). Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action. Hum Reprod, 14, 1445-8.
  • Bray, G.A. (1997). Obesity and reproduction. Hum Reprod, 12, 26-32.
  • Brito, L., Barth, A., Rawlings, N., Wilde, R., Crews, D.Jr., Mir, P., & Kastelic, J. (2007). Circulating metabolic hormones during the peripubertal period and their association with testicular development in bulls. Reprod Domest Anim, 42, 502-8.
  • Caldefie-Chezet, F., Poulin, A., Tridon, A., Sion, B., & Vasson, M.P. (2001). Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J Leukoc Biol, 69, 414-8.
  • Camiña, J.P., Lage, M., Menendez, C., Graña, M., García-Devesa, J., Dieguez, C., & Casanueva, F.F. (2002). Evidence of free leptin in human seminal plasma. Endocrine, 17, 169-74.
  • Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., & Burn, P. (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269, 546-9.
  • Caprio, M., Fabbrini, E., Isidori, A.M., Aversa, A., & Fabbri, A. (2001). Leptin in reproduction. Trends Endocrinol Metab, 12, 65-72.
  • Caprio, M., Fabbrini, E., Ricci, G., Basciani, S., Gnessi, L., Arizzi, M., Carta, A.R., De Martino, M.U., Isidori, A.M., Frajese, G.V., & Fabbri, A. (2003). Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod, 68, 1199-207.
  • Caprio, M., Isidori, A.M., Carta, A.R., Moretti, C., Dufau, M.L., & Fabbri, A. (1999). Expression of functional leptin receptors in rodent Leydig cells. Endocrinology, 140, 4939-47.
  • Cervero, A., Horcajadas, J.A., Domínguez, F., Pellicer, A., & Simón, C. (2005). Leptin system in embryo development and implantation: a protein in search of a function. Reprod Biomed Online, 10, 217-23.
  • Chavarro, J.E., Toth, T.L., Wright, D.L., Meeker, J.D., & Hauser, R. (2010). Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril, 93, 2222-31.
  • Chehab, F.F., Lim, M.E., & Lu, R. (1996). Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet, 12, 318-20.
  • Chehab, F.F., Mounzih, K., Lu, R., & Lim, M.E. (1997). Early onset of reproductive function in normal female mice treated with leptin. Science, 275, 88-90.
  • Chelikani, P.K., Ambrose, J.D., Keisler, D.H., & Kennelly, J.J. (2004). Effect of short-term fasting on plasma concentrations of leptin and other hormones and metabolites in dairy cattle. Domest Anim Endocrinol, 26, 33-48.
  • Chen, H., Charlat, O., Tartaglia, L.A., Woolf, E.A., Weng, X., Ellis, S.J., Lakey, N.D., Culpepper, J., Moore, K.J., Breitbart, R.E., Duyk, G.M., Tepper, R.I., & Morgenstern, J.P. (1996). Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell, 84, 491-5.
  • Cheung, C.C., Thornton, J.E., Nurani, S.D., Clifton, D.K., & Steiner, R.A. (2001). A reassessment of leptin's role in triggering the onset of puberty in the rat and mouse. Neuroendocrinology, 74, 12-21.
  • Chilliard, Y., Bonnet, M., Delavaud, C., Faulconnier, Y., Leroux, C., Djiane, J., & Bocquier, F. (2001). Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration. Domest Anim Endocrinol, 21, 271-95.
  • Cioffi, J.A., Van Blerkom, J., Antczak, M., Shafer, A., Wittmer, S., & Snodgrass, H.R. (1997). The expression of leptin and its receptors in pre-ovulatory human follicles. Mol Hum Reprod, 3, 467-72.
  • Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.M., Basdevant, A., Bougnères, P., Lebouc, Y., Froguel, P., & Guy-Grand, B. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392, 398-401.
  • Cowley, M.A., Smart, J.L., Rubinstein, M., Cerdán, M.G., Diano, S., Horvath, T.L., Cone, R.D., & Low, M.J. (2001). Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature, 411, 480-4.
  • Craig, J.A., Zhu, H., Dyce, P.W., Wen, L., & Li, J. (2005). Leptin enhances porcine preimplantation embryo development in vitro. Mol Cell Endocrinol, 229, 141-7.
  • Cunningham, M.J., Clifton, D.K., & Steiner, R.A. (1999). Leptin's actions on the reproductive axis: perspectives and mechanisms. Biol Reprod, 60, 216-22.
  • Dayi, A., Bediz, C.S., Musal, B., Yilmaz, O., Comlekci, A., Celiloglu, M., & Cimrin, D. (2005).Comparison of leptin levels in serum and follicular fluid during the oestrous cycle in cows. Acta Vet Hung, 53, 457-67. De Ambrogi, M., Spinaci, M., Galeati, G., & Tamanini, C. (2007). Leptin receptor in boar spermatozoa. Int J Androl, 30, 458-61.
  • De Lamirande, E., & Gagnon, C. (1995). Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod.;10:15-21.
  • Doğrutekin, D., Çetin, M., & Udum, C.D. (2008). Relations between leptin and testosterone and glucose concentrations, fattening performance and reproductive development in growing bulls. J Biol Environ Sci, 2.
  • Dorn, C., Reinsberg, J., Kupka, M., Van der Ven, H., & Schild, R.L. (2003). Leptin, VEGF, IGF-1, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization. Arch Gynecol Obstet, 268, 187-93.
  • Dos Santos, E., Serazin, V., Morvan, C., Torre, A., Wainer, R., de Mazancourt, P., & Dieudonné, M.N. (2012). Adiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril, 97, 771-8.e1.
  • Duggal, P.S., Van Der Hoek, K.H., Milner, C.R., Ryan, N.K., Armstrong, D.T., Magoffin, D.A., & Norman, R.J. (2000). The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology, 141, 1971-6.
  • Dundar, N.O., Anal, O., Dundar, B., Ozkan, H., Caliskan, S., & Büyükgebiz, A. (2005). Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants. J Pediatr Endocrinol Metab, 18, 181-7.
  • Dyer, C.J., Simmons, J.M., Matteri, R.L., & Keisler, D.H. (1997). Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well-fed and feed-restricted ewes. Domest Anim Endocrinol, 14, 119-28.
  • Ebihara, K., Ogawa, Y., Isse, N., Mori, K., Tamura, N., Masuzaki, H., Kohno, K., Yura, S., Hosoda, K., Sagawa, N., & Nakao, K. (1997). Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription. Biochem Biophys Res Commun, 241, 658-63.
  • Ehrhardt, R.A., Slepetis, R.M., Bell, A.W., & Boisclair, Y.R. (2001). Maternal leptin is elevated during pregnancy in sheep. Domest Anim Endocrinol, 21, 85-96.
  • Ehrhardt, R.A., Slepetis, R.M., Siegal-Willott, J., Van Amburgh, M.E., Bell, A.W., & Boisclair, Y.R. (2000). Development of a specific radioimmunoassay to measure physiological changes of circulating leptin in cattle and sheep. J Endocrinol, 166, 519-28.
  • El-Badry, D.A., Gamal, A., & El-Maaty, A.M.A. (2016). Seminal plasma hormonal profile of Arabian stallions that are classified ‘good’or ‘poor’for semen freezing. Asian Pac J Reprod, 5,453-8.
  • Escobar-Morreale, H.F., Escobar del Rey, F., & Morreale de Escobar, G. (1997). Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology, 138, 4485-8.
  • Farooqi, I.S., Jebb, S.A, Langmack, G., Lawrence, E., Cheetham, C.H., Prentice, A.M., Hughes, I.A., McCamish, M.A., & O'Rahilly, S. (1999). Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med, 341, 879-84.
  • Fei, H., Okano, H.J., Li, C., Lee, G.H., Zhao, C., Darnell, R., & Friedman, J.M. (1997). Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci U S A, 94, 7001-5.
  • Fejes, I., Koloszár, S., Závaczki, Z., Daru, J., Szöllösi, J., & Pál, A. (2006). Effect of body weight on testosterone/estradiol ratio in oligozoospermic patients. Arch Androl, 52, 97-102.
  • Fernandez, C.D., Fernandes, G.S., Favareto, A.P., Perobelli, J.E., Sanabria, M., & Kempinas, W.D. (2017). Decreased Implantation Numbceer After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure. Reprod Sci, 24, 234-241.
  • Florkowski, C.M., Collier, G.R., Zimmet, P.Z., Livesey, J.H., Espiner, E.A., & Donald, R.A. (1996). Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol (Oxf), 45, 769-73.
  • Fontoura, P., Mello, M.D., Gallo-Sá, P., Erthal-Martins, M.C., Cardoso, M.C., & Ramos, C. (2017). Leptin Improves Sperm Cryopreservation via Antioxidant Defense. J Reprod Infertil, 18, 172-8.
  • Fortuño, A., Bidegain, J., Baltanás, A., Moreno, M.U., Montero, L., Landecho, M.F., Beloqui, O., Díez, J., & Zalba, G. (2010). Is leptin involved in phagocytic NADPH oxidase overactivity in obesity? Potential clinical implications. J Hypertens, 28, 1944-50.
  • Frederich, R.C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B.B., & Flier, J.S. (1995). Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med, 1, 1311-4.
  • Frühbeck, G. (2006). Intracellular signalling pathways activated by leptin. Biochem J, 393, 7-20.
  • Gainsford, T., Willson, T.A., Metcalf, D., Handman, E., McFarlane, C., Ng, A., Nicola, N.A., Alexander, W.S., & Hilton, D.J. (1996). Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A, 93, 14564-8.
  • Gao, Y., Zhao, G., Song, Y., Haire, A., Yang, A., Zhao, X., & Wusiman, A. (2022). Presence of leptin and its receptor in the ram reproductive system and in vitro effect of leptin on sperm quality. PeerJ, 26, 10, e13982.
  • Garcia, M.R., Amstalden, M., Williams, S.W., Stanko, R.L., Morrison, C.D., Keisler, D.H., Nizielski, S.E., & Williams, G.L. (2002). Serum leptin and its adipose gene expression during pubertal development, the estrous cycle, and different seasons in cattle. J Anim Sci, 80, 2158-67.
  • Garcia-Mayor, R.V., Andrade, M.A., Rios, M., Lage, M., Dieguez, C., & Casanueva, F.F. (1997). Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab, 82, 2849-55.
  • Gentry, G.T.Jr., Gentry, L.R., & Godke, R.A. (2013). The effect of exogenous follicle stimulating hormone (FSH) and endogenous plasma leptin concentrations on the pregnancy rate of beef heifers subjected to fixed-timed artificial insemination (FTAI). Anim Reprod Sci, 138, 49-54.
  • Glander, H.J., Lammert, A., Paasch, U., Glasow, A., & Kratzsch, J. (2002). Leptin exists in tubuli seminiferi and in seminal plasma. Andrologia, 34, 227-33.
  • Gogga, P., Karbowska, J., Meissner, W., & Kochan, Z. (2011). Rola leptyny w regulacji metabolizmu lipidów i węglowodanów [Role of leptin in the regulation of lipid and carbohydrate metabolism]. Postepy Hig Med Dosw (Online), 65, 255-62.
  • Gong, Y., Luo, Z., Zhu, Q.L., Zheng, J.L., Tan, X.Y., Chen, Q.L., Lin, Y.C., & Lu, R.H. (2013). Characterization and tissue distribution of leptin, leptin receptor and leptin receptor overlapping transcript genes in yellow catfish Pelteobagrus fulvidraco. Gen Comp Endocrinol, 182, 1-6.
  • Gonnelli, S., Caffarelli, C., & Nuti, R. (2014). Obesity and fracture risk. Clin Cases Miner Bone Metab, 11, 9-14. González, R.R., Caballero-Campo, P., Jasper, M., Mercader, A., Devoto, L., Pellicer, A., & Simon, C. (2000). Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab, 85, 4883-8.
  • Gorska, E., Popko, K., Stelmaszczyk-Emmel, A., Ciepiela, O., Kucharska, A., & Wasik, M. (2010). Leptin receptors. Eur J Med Res, 15, 50-4.
  • Goumenou, A.G., Matalliotakis, I.M., Koumantakis, G.E., & Panidis, D.K. (2003). The role of leptin in fertility. Eur J Obstet Gynecol Reprod Biol, 106, 118-24.
  • Grauz, N.M., Laluoi, M., Perroz, D.D., Raposinho, P.D., Blum, W.F., & Aubert, M.L. (1998). Failure of leptin administration to advance sexual maturation in the female rat. In Proceedings of the 80th Meeting of the Endo Soc., New Orleans, Louisiana.
  • Green, E.D., Maffei, M., Braden, V.V., Proenca, R., DeSilva, U., Zhang, Y., Chua, S.C.Jr., Leibel, R.L., Weissenbach, J., & Friedman, J.M. (1995). The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7. Genome Res, 5:5-12.
  • Grumbach, M.M., & Styne. D.M. (1998). Puberty: ontogeny, neuroendocrinology, physiology, and disorders. Williams textbook of endocrinology, 9, e1625.
  • Gualillo, O., Lago. F., García, M., Menéndez, C., Señarís. R., Casanueva, F.F., & Diéguez, C. (1999). Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology, 140, 5149-53.
  • Guerra, B., Santana, A., Fuentes, T., Delgado-Guerra, S., Cabrera-Socorro, A., Dorado, C., & Calbet, J.A. (2007). Leptin receptors in human skeletal muscle. J Appl Physiol (1985), 102, 1786-92.
  • Halaas, J.L., Gajiwala, K.S., Maffei, M., Cohen, S.L., Chait, B.T., Rabinowitz, D., Lallone, R.L., Burley, S.K., & Friedman, J.M. (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269, 543-6.
  • Hamada, A., Esteves, S.C., & Agarwal, A. (2011). Unexplained male infertility: potential causes and management. Hum Androl, 1, 2-16.
  • Hamann, A., & Matthaei, S. (1996). Regulation of energy balance by leptin. Exp Clin Endocrinol Diabetes, 104, 293-300.
  • Hammoud, A.O., Gibson, M., Peterson, C.M., Meikle, A.W., & Carrell, D.T. (2008). Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril, 90, 897-904.
  • Hardie, L., Trayhurn, P., Abramovich, D., & Fowler, P. (1997). Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol (Oxf), 47, 101-6.
  • Haron, M.N., D'Souza, U.J., Jaafar, H., Zakaria, R., & Singh, H.J. (2010). Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats. Fertil Steril, 93, 322-4.
  • Hauguel-de Mouzon, S., Lepercq, J., & Catalano, P. (2006). The known and unknown of leptin in pregnancy. Am J Obstet Gynecol, 194, 1537-45.
  • Henson, M.C., & Castracane, V.D. (2006). Leptin in pregnancy: an update. Biol Reprod, 74, 218-29.
  • Henson, M.C., & Castracane, V.D. (2000). Leptin in pregnancy. Biol Reprod, 63, 1219-28.
  • Herrid, M., Palanisamy, S.K., Ciller, U.A., Fan, R., Moens, P., Smart, N.A., & McFarlane, J.R. (2014). An updated view of leptin on implantation and pregnancy: a review. Physiol Res, 63, 543-57.
  • Highman, T.J., Friedman, J.E., Huston, L.P., Wong, W.W., & Catalano, P.M. (1998). Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. Am J Obstet Gynecol, 178, 1010-5.
  • Hofny, E.R., Ali, M.E., Abdel-Hafez, H.Z., Kamal, Eel-D., Mohamed, E.E., Abd El-Azeem, H.G., & Mostafa, T. (2010). Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril, 94, 581-4.
  • Hoggard, N., Mercer, J.G., Rayner, D.V., Moar, K., Trayhurn, P., & Williams, L.M. (1997). Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem Biophys Res Commun, 232, 383-7.
  • Holness, M.J., Munns, M.J., & Sugden, M.C. (1999). Current concepts concerning the role of leptin in reproductive function. Mol Cell Endocrinol, 157, 11-20.
  • Houseknecht, K.L., Baile, C.A., Matteri, R.L., & Spurlock, M.E. (1998). The biology of leptin: a review. J Anim Sci, 76, 1405-20.
  • Houseknecht, K.L., & Portocarrero, C.P. (1998). Leptin and its receptors: regulators of whole-body energy homeostasis. Domest Anim Endocrinol, 15, 457-75.
  • Idelevich, A., Sato, K., & Baron, R. (2013). What are the effects of leptin on bone and where are they exerted? J Bone Miner Res, 28, 18-21.
  • Iikuni, N., Lam, Q.L., Lu, L., Matarese, G., & La Cava, A. (2008). Leptin and Inflammation. Curr Immunol Rev, 4, 70-79.
  • Iqbal, J., Pompolo, S., Murakami, T., Grouzmann, E., Sakurai, T., Meister, B., & Clarke, I.J. (2001). Immunohistochemical characterization of localization of long-form leptin receptor (OB-Rb) in neurochemically defined cells in the ovine hypothalamus. Brain Res, 920, 55-64.
  • Ishikawa, T., Fujioka, H., Ishimura, T., Takenaka, A., & Fujisawa, M. (2007). Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia, 39, 22-7. Isidori, A.M., Caprio, M., Strollo, F., Moretti, C., Frajese, G., Isidori, A., & Fabbri, A. (1999). Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab, 84, 3673-80.
  • Jahan, S., Bibi, R., Ahmed, S., & Kafeel, S. (2011). Leptin levels in infertile males. J Coll Physicians Surg Pak, 21, 393-7.
  • Jensen, T.K., Andersson, A.M., Jørgensen, N., Andersen, A.G., Carlsen, E., Petersen, J.H., & Skakkebaek, N.E. (2004). Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril, 82, 863-70.
  • Jia, Z., Zhang, J., Wu, Z., & Tian, J. (2012). Leptin enhances maturation and development of calf oocytes in vitro. Reprod Domest Anim, 47, 718-23.
  • Jin, L., Burguera, B.G., Couce, M.E., Scheithauer, B.W., Lamsan, J., Eberhardt, N.L., Kulig, E., & Lloyd, R.V. (1999). Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab, 84, 2903-11.
  • Johnson, L., Thompson, D.L.Jr., & Varner, D.D. (2008). Role of Sertoli cell number and function on regulation of spermatogenesis. Anim Reprod Sci, 105, 23-51.
  • Jope, T., Lammert, A., Kratzsch, J., Paasch, U., & Glander, H.J. (2003). Leptin and leptin receptor in human seminal plasma and in human spermatozoa. Int J Androl, 26, 335-41.
  • Jung, C.H., & Kim, M.S. (2013). Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res, 36, 201-7.
  • Karlsson, C., Lindell, K., Svensson, E., Bergh, C., Lind, P., Billig, H., Carlsson, L.M., & Carlsson, B. (1997). Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab, 82, 4144-8.
  • Kemal Duru, N., Morshedi, M., & Oehninger, S. (2000). Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril, 74, 1200-7.
  • Khaki, A., Batavani, R.A., & Najafi, G. (2013). The in vitro effect of leptin on semen quality of water buffalo (Bubalus bubalis) bulls. Vet Res Forum, 4:7-12.
  • Kieffer, T.J., Heller, R.S., & Habener, J.F. (1996). Leptin receptors expressed on pancreatic beta-cells. Biochem Biophys Res Commun, 224, 522-7.
  • Kieffer, T.J., Heller, R.S., Leech, C.A., Holz, G.G., & Habener, J.F. (1997). Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes, 46, 1087-93.
  • Kiess, W., Blum, W.F., & Aubert, M.L. (1998). Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. Eur J Endocrinol, 138, 26-9.
  • Kitawaki, J., Koshiba, H., Ishihara, H., Kusuki, I., Tsukamoto, K., & Honjo, H. (2000). Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab, 85, 1946-50.
  • Kokkonen, T., Taponen, J., Anttila, T., Syrjälä-Qvist, L., Delavaud, C., Chilliard, Y., Tuori, M., & Tesfa, A.T. (2005). Effect of body fatness and glucogenic supplement on lipid and protein mobilization and plasma leptin in dairy cows. J Dairy Sci, 88, 1127-41.
  • Kolaczynski, J.W., Ohannesian, J.P., Considine, R.V., Marco, C.C., & Caro, J.F. (1996). Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab, 81, 4162-5.
  • Kort, H.I., Massey, J.B., Elsner, C.W., Mitchell-Leef, D., Shapiro, D.B., Witt, M.A., & Roudebush, W.E. (2006). Impact of body mass index values on sperm quantity and quality. J Androl, 27, 450-2.
  • Küçükkurt, İ. (2015). Leptin ve Diğer Hormonlar Üzerindeki Etkileri. Kocatepe Vet J, 8, 75-83.
  • Kulcsár, M., Dankó, G., Magdy, H.G., Reiczigel, J., Forgach, T., Proháczik, A., Delavaud, C., Magyar, K., Chilliard, Y., Solti, L., & Huszenicza, G. (2006). Pregnancy stage and number of fetuses may influence maternal plasma leptin in ewes. Acta Vet Hung, 54, 221-34.
  • Kumar, P., Saini, M., Kumar, D., Jan, M.H., Swami, D.S., & Sharma, R.K. (2016). Quantification of leptin in seminal plasma of buffalo bulls and its correlation with antioxidant status, conventional and computer-assisted sperm analysis (CASA) semen variables. Anim Reprod Sci, 166, 122-7.
  • La Cava, A., Alviggi, C., & Matarese, G. (2004). Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med (Berl), 82, 4-11.
  • Lackey, B.R., Gray, S.L., & Henricks, D.M. (2002). Measurement of leptin and insulin-like growth factor-I in seminal plasma from different species. Physiol Res, 51, 309-11.
  • Lago, R., Gómez, R., Lago, F., Gómez-Reino, J., & Gualillo, O. (2008). Leptin beyond body weight regulation--current concepts concerning its role in immune function and inflammation. Cell Immunol, 252, 139-45. Lampiao, F., & du Plessis, S.S. (2008). Insulin and leptin enhance human sperm motility, acrosome reaction and nitric oxide production. Asian J Androl, 10, 799-807.
  • Lange-Consiglio, A., Corradetti, B., Perrini, C., Bizzaro, D., & Cremonesi, F. (2016). Leptin and leptin receptor are detectable in equine spermatozoa but are not involved in in vitro fertilisation. Reprod Fertil Dev, 28, 574-85.
  • Lappas, M., Yee, K., Permezel, M., & Rice, G.E. (2005). Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies. J Endocrinol, 186, 457-65.
  • Mangian, H.F., Lee, R.G., Paul, G.L., Emmert, J.L., & Shay, N.F. (1998). Zinc deficiency suppresses plasma leptin concentrations in rats. The Journal of Nutritional Biochemistry, 9, 47-51.
  • Pradnyana, D.I.L., Pemayun, T.G., Damriyasa, I.M., & Dharmawan, N.S. (2016). Administration of leptin increases the level of Follicle Stimulating Hormone (FSH) and development of ovarian follicles in postpartum anestrus of Bali cattle. Bali Med J, 5, 69-73.
  • Reittuzzi, G., & Faggioni, R. (2000). Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol, 68, 437-46.
  • Lea, R.G., Howe, D., Hannah, L.T., Bonneau, O., Hunter, L., & Hoggard, N. (2000). Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod, 6, 763-9.
  • Lee, J.A., Kuchakulla, M., Arora, H., Kulandavelu, S., Gonzalez, E., Masterson, T.A., Hare, J.M., Kaiser, U.B., & Ramasamy, R. (2019). Age Induced Nitroso-Redox Imbalance Leads to Subclinical Hypogonadism in Male Mice. Front Endocrinol (Lausanne), 10, 190.
  • Lepercq, J., Challier, J.C., Guerre-Millo, M., Cauzac, M., Vidal, H., & Hauguel-de Mouzon, S. (2001). Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab, 86, 2409-13.
  • Li, H.W., Chiu, P.C., Cheung, M.P., Yeung, W.S., & O, W.S. (2009). Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa. Int J Androl, 32, 687-94.
  • Li, X.X., Lee, D.S., Kim, K.J., Lee, J.H., Kim, E.Y., Park, J.Y., & Kim, M.K. (2013). Leptin and nonessential amino acids enhance porcine preimplantation embryo development in vitro by intracytoplasmic sperm injection. Theriogenology, 79, 291-8.
  • Linnemann, K., Malek, A., Schneider, H., & Fusch, C. (2001). Physiological and pathological regulation of feto/placento/maternal leptin expression. Biochem Soc Trans, 29, 86-90.
  • Luukkaa, V., Pesonen, U., Huhtaniemi, I., Lehtonen, A., Tilvis, R., Tuomilehto, J., Koulu, M., & Huupponen, R. (1998). Inverse correlation between serum testosterone and leptin in men. J Clin Endocrinol Metab, 83, 3243-6.
  • Macedo, T.J.S., Santos, J.M.S., Bezerra, M.É.S., Menezes, V.G., Gouveia, B.B., Barbosa, L.M.R., Lins, T.L.B.G., Monte, A.P.O., Barberino, R.S., Batista, A.M., Barros, V.R.P., Wischral, A., Queiroz, M.A.A., Araújo, G.G.L., & Matos, M.H.T. (2019). Immunolocalization of leptin and its receptor in the sheep ovary and in vitro effect of leptin on follicular development and oocyte maturation. Mol Cell Endocrinol, 495, 110506.
  • Maciel, M.N., Zieba, D.A., Amstalden, M., Keisler, D.H., Neves, J.P., & Williams, G.L. (2004). Chronic administration of recombinant ovine leptin in growing beef heifers: effects on secretion of LH, metabolic hormones, and timing of puberty. J Anim Sci, 82, 2930-6.
  • Maciel, M.N., Zieba, D.A., Amstalden, M., Keisler, D.H., Neves, J.P., & Williams, G.L. (2004). Leptin prevents fasting-mediated reductions in pulsatile secretion of luteinizing hormone and enhances its gonadotropin-releasing hormone-mediated release in heifers. Biol Reprod, 70, 229-35.
  • Maffei, M., Halaas, J., Ravussin, E., Pratley, R.E., Lee, G.H., Zhang, Y., Fei, H., Kim, S., Lallone, R., & Ranganathan S. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1, 1155-61.
  • Mahfouz, R.Z., du Plessis, S.S., Aziz, N., Sharma, R., Sabanegh, E., & Agarwal, A. (2010). Sperm viability, apoptosis, and intracellular reactive oxygen species levels in human spermatozoa before and after induction of oxidative stress. Fertil Steril, 93, 814-21.
  • Malik, N.M., Carter, N.D., Murray, J.F., Scaramuzzi, R.J., Wilson, C.A., & Stock, M.J. (2001). Leptin requirement for conception, implantation, and gestation in the mouse. Endocrinology, 142(12), 5198-202.
  • Smith, G.D., Jackson, L.M., & Foster, D.L. (2002). Leptin regulation of reproductive function and fertility. Theriogenology, 57(1), 73-86.
  • Malik, I.A., Durairajanayagam, D., & Singh, H.J. (2019). Leptin and its actions on reproduction in males. Asian J Androl, 21(3), 296-299.
  • Mangian, H.F., Lee, R.G., Paul, G.L., Emmert, J.L., & Shay, N.F. (1998). Zinc deficiency suppresses plasma leptin concentrations in rats. J Nut Biochem, 9, 47-51.
  • Mantzoros, C.S., Ozata, M., Negrao, A.B., Suchard, M.A., Ziotopoulou, M., Caglayan, S., Elashoff, R.M., Cogswell, R.J., Negro, P., Liberty, V., Wong, M.L., Veldhuis, J., Ozdemir, I.C., Gold, P.W., Flier, J.S., & Licinio, J. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab. 2001, 86, 3284-91.
  • Mantzoros, C.S. (2000). Role of leptin in reproduction. Ann N Y Acad Sci, 900, 174-83.
  • Marik, P.E. Leptin, obesity, and obstructive sleep apnea. Chest. 2000;118:569-71.
  • Martins, A.D., Moreira, A.C., Sá, R., Monteiro, M.P., Sousa, M., Carvalho, R.A., Silva, B.M., Oliveira, P.F., & Alves, M.G. (2015). Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta, 1852, 1824-32.
  • Martins, F.F., Aguila, M.B., & Mandarim-de-Lacerda, C.A. (2017). Impaired steroidogenesis in the testis of leptin-deficient mice (ob/ob -/-). Acta Histochem, 119, 508-515.
  • Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Yoshimasa, Y., Tanaka, I., Mori, T., & Nakao, K. (1997). Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med, 3, 1029-33.
  • McMillen, I.C., Edwards, L.J., Duffield, J., & Muhlhausler, B.S. (2006). Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction, 131, 415-27.
  • Mercer, J.G., Moar, K.M., Findlay, P.A., Hoggard, N., & Adam, C.L. (1998). Association of leptin receptor (OB-Rb), NPY and GLP-1 gene expression in the ovine and murine brainstem. Regul Pept, 75-76, 271-8.
  • Montague, C.T., Prins, J.B., Sanders, L., Digby, J.E., & O'Rahilly, S. (1997). Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes, 46, 342-7.
  • Morrison, C.D., Daniel, J.A., Holmberg, B.J., Djiane, J., Raver, N., Gertler, A., & Keisler, D.H. (2001). Central infusion of leptin into well-fed and undernourished ewe lambs: effects on feed intake and serum concentrations of growth hormone and luteinizing hormone. J Endocrinol, 168, 317-24.
  • Mounzih, K., Lu, R., & Chehab, F.F. (1997). Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology, 138, 1190-3.
  • Mukherjea, R., Castonguay, T.W., Douglass, L.W., & Moser-Veillon, P. (1999). Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization. Life Sci, 65, 183-93.
  • Nagatani, S., Zeng, Y., Keisler, D.H., Foster, D.L., & Jaffe, C.A. (2000). Leptin regulates pulsatile luteinizing hormone and growth hormone secretion in the sheep. Endocrinology, 141, 3965-75.
  • Nikbakht, G., Mehr, M.R., Baghbanzadeh, A., Tajik, P., Tamanini, C., & Emam, M. (2010). Leptin receptor mRNA in bull ejaculated spermatozoa. Reprod Domest Anim, 45, 237-42.
  • Ogueh, O., Sooranna, S., Nicolaides, K.H., & Johnson, M.R. (2000). The relationship between leptin concentration and bone metabolism in the human fetus. J Clin Endocrinol Metab, 85, 1997-9.
  • Palmert, M.R., Radovick, S., & Boepple, P.A. (1998). The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. J Clin Endocrinol Metab, 83, 1091-6.
  • Parent, A.S., Lebrethon, M.C., Gérard, A., Vandersmissen, E., & Bourguignon, J.P. (2000). Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y. Regul Pept, 92, 17-24.
  • Paz-Filho, G., Delibasi, T., Erol, H.K., Wong, M.L., & Licinio, J. (2009). Congenital leptin deficiency and thyroid function. Thyroid Res, 2, 11.
  • Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269, 540-3.
  • Pérez-Pérez, A., Sánchez-Jiménez, F., Maymó, J., Dueñas, J.L., Varone, C., & Sánchez-Margalet, V. (2015). Role of leptin in female reproduction. Clin Chem Lab Med, 53, 15-28.
  • Rago, V., Aquila, S., Guido, C., & Carpino, A. (2009). Leptin and its receptor are expressed in the testis and in the epididymis of young and adult pigs. Anat Rec (Hoboken), 292, 736-45.
  • Reitman, M.L., Bi, S., Marcus-Samuels, B., & Gavrilova, O. (2001). Leptin and its role in pregnancy and fetal development-an overview. Biochem Soc Trans, 29, 68-72.
  • Ren, M.Q., Wegner, J., Bellmann, O., Brockmann, G.A., Schneider, F., Teuscher, F., & Ender, K. (2002). Comparing mRNA levels of genes encoding leptin, leptin receptor, and lipoprotein lipase between dairy and beef cattle. Domest Anim Endocrinol, 23, 371-81.
  • Rosenbaum, M., & Leibel, R.L. (1999). Clinical review 107: Role of gonadal steroids in the sexual dimorphisms in body composition and circulating concentrations of leptin. J Clin Endocrinol Metab, 84, 1784-9.
  • Sadock, V., Sadock, B., & Ruiz, P. (2003). Synopsis of psychiatry: behavioral sciences-clinical psychology. Translated by Rafiee H, Sobhanian K. Tehran: Arjmand Publication.
  • Sagawa, N., Yura, S., Itoh, H., Mise, H., Kakui, K., Korita, D., Takemura, M., Nuamah, M.A., Ogawa, Y., Masuzaki, H., Nakao, K., & Fujii, S. (2002). Role of leptin in pregnancy-a review. Placenta, 23, S80-6.
  • Sahu, A. (2003). Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. Front Neuroendocrinol, 24, 225-53.
  • Sáinz, N., Barrenetxe, J., Moreno-Aliaga, M.J., & Martínez, J.A. (2015). Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64, 35-46.
  • Sattar, N., Greer, I.A., Pirwani, I., Gibson, J., & Wallace, A.M. (1998). Leptin levels in pregnancy: marker for fat accumulation and mobilization? Acta Obstet Gynecol Scand, 77, 278-83.
  • Scaramuzzi, R.J., & Martin, G.B. (2008). The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone-free methods for controlling fertility. Reprod Domest Anim, 43, 129-36.
  • Schinzari, F., Tesauro, M., Rovella, V., Di Daniele, N., Mores, N., Veneziani, A., & Cardillo, C. (2013). Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome. J Clin Endocrinol Metab, 98, 1235-41.
  • Schroeter, M.R., Leifheit-Nestler, M., Hubert, A., Schumann, B., Glückermann, R., Eschholz, N., Krüger, N., Lutz, S., Hasenfuss, G., Konstantinides, S., & Schäfer, K. (2013). Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains. Cardiovasc Res, 99, 555-65.
  • Schubring, C., Englaro, P., Siebler, T., Blum, W.F., Demirakca, T., Kratzsch, J., & Kiess, W. (1998). Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels. Horm Res, 50, 276-83.
  • Schubring, C., Prohaska, F., Prohaska, A., Englaro, P., Blum, W., Siebler, T., Kratzsch, J., & Kiess, W. (1999). Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry. Eur J Obstet Gynecol Reprod Biol, 86, 151-7.
  • Sharma, K., & Considine, R.V. (1998). The Ob protein (leptin) and the kidney. Kidney Int, 53, 1483-7.
  • Shimizu, H., Shimomura, Y., Nakanishi, Y., Futawatari, T., Ohtani, K., Sato, N., & Mori, M. (1997). Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol, 154, 285-92.
  • Shiraishi, K., & Naito, K. (2007). Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol, 178, 1012-7.
  • Singh, B., Prasad, S., & Gupta, H.P. (2012). Effect of leptin on in-vitro maturation of oocytes and on early embryonic development in buffaloes. Indian J Anim Reprod, 33, 1-6.
  • Singhal, A., Farooqi, I.S., O'Rahilly, S., Cole, T.J., Fewtrell, M., & Lucas, A. (2002). Early nutrition and leptin concentrations in later life. Am J Clin Nutr, 75, 993-9.
  • Slieker, L.J., Sloop, K.W., Surface, P.L., Kriauciunas, A., LaQuier, F., Manetta, J., Bue-Valleskey, J., & Stephens, T.W. (1996). Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem, 271, 5301-4.
  • Smith, J.T., & Waddell, B.J. (2003). Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids. Endocrinology, 144, 3024-30.
  • Smith, J.T., & Waddell, B.J. (2002). Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids. Biol Reprod, 67, 1204-10.
  • Sobhani, I., Bado, A., Vissuzaine, C., Buyse, M., Kermorgant, S., Laigneau, J.P., Attoub, S., Lehy, T., Henin, D., Mignon, M., & Lewin, M.J. (2000). Leptin secretion and leptin receptor in the human stomach. Gut, 47, 178-83.
  • Solinas, G. (2010). Leptin signalling coordinates lipid oxidation with thermogenesis and defence against oxidative stress. Clin Exp Pharmacol Physiol, 37, 953-4.
  • Stone, R.T., Kappes, S.M., & Beattie, C.W. (1996). The bovine homolog of the obese gene maps to chromosome 4. Mamm Genome, 7, 399-400.
  • Strobel, A., Issad, T., Camoin, L., Ozata, M., & Strosberg, A.D. (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet, 18, 213-5.
  • Sullivan, S.D., & Moenter, S.M. (2004). Gamma-aminobutyric acid neurons integrate and rapidly transmit permissive and inhibitory metabolic cues to gonadotropin-releasing hormone neurons. Endocrinology, 145, 1194-202.
  • Swain, J.E., Dunn, R.L., McConnell, D., Gonzalez-Martinez, J., & Smith, G.D. (2004). Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development. Biol Reprod, 71, 1446-52.
  • Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., Smutko, J.S., Mays, G.G., Wool, E.A., Monroe, C.A., & Tepper, R.I. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell, 83, 1263-71.
  • Tena-Sempere, M., Pinilla, L., González, L.C., Diéguez, C., Casanueva, F.F., & Aguilar, E. (1999). Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol, 161, 211-8.
  • Thomas, M.G., Enns, R.M., Hallford, D.M., Keisler, D.H., Obeidat, B.S., Morrison, C.D., Hernandez, J.A., Bryant, W.D., Flores, R., Lopez, R., & Narro, L. (2002). Relationships of metabolic hormones and serum glucose to growth and reproductive development in performance-tested Angus, Brangus, and Brahman bulls. J Anim Sci, 80, 757-67.
  • Trayhurn, P., Thomas, M.E., Duncan, J.S., & Rayner, D.V. (1995). Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice. FEBS Lett, 368, 488-90.
  • Wallace, A.M. (2000). Measurement of leptin and leptin binding in the human circulation. Ann Clin Biochem, 37, 244-52.
  • Wang, Y.Y., Wang, Y.L., Li, H.P., Zhu, H.S., Jiang,.Q.D., Zhang, L., Wang, L.F., Han, L.Q., Zhong, K., Guo, Y.J., Lu, W.F., Li, H.J., & Yang, G.Y. (2011). Leptin mRNA expression in the rat mammary gland at different activation stages. Genet Mol Res, 10, 3657-63.
  • Wang, X., Zhang, X., Hu, L., & Li, H. (2018). Exogenous leptin affects sperm parameters and impairs blood testis barrier integrity in adult male mice. Reprod Biol Endocrinol, 16(1), 55.
  • Wannamethee, S.G., Shaper, A.G., Whincup, P.H., Lennon, L., & Sattar, N. (2013). Adiposity, adipokines, and risk of incident stroke in older men. Stroke, 44, 3-8.
  • Weir, C.P., & Robaire, B. (2007). Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. J Androl, 28, 229-40.
  • Wells, J.C. (2007). Sexual dimorphism of body composition. Best Pract Res Clin Endocrinol Metab, 21, 415-30. Williams, G.L., Amstalden, M., Garcia, M.R., Stanko, R.L., Nizielski, S.E., Morrison, C.D., & Keisler, D.H. (2002). Leptin and its role in the central regulation of reproduction in cattle. Domest Anim Endocrinol, 23, 339-49.
  • Wolsk, E., Mygind, H., Grøndahl, T.S., Pedersen, B.K., & van Hall, G. (2012). Human skeletal muscle releases leptin in vivo. Cytokine, 60, 667-73.
  • Yamagishi, S., Amano, S., Inagaki, Y., Okamoto, T., Takeuchi, M., & Inoue, H. (2003). Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res, 65, 186-90.
  • Yu, W.H., Kimura, M., Walczewska, A., Karanth, S., & McCann, S.M. (1997). Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci U S A, 94, 1023-8.
  • Yuan, M., Huang, G., Li, J., Zhang, J., Li, F., Li, K., Gao, B., Zeng, L., Shan, W., Lin, P., & Huang, L. (2014). Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process. Reprod Biol Endocrinol, 12, 15.
  • Zegers-Hochschild, F., Adamson, G.D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., Rienzi, L., Sunde, A., Schmidt, L., Cooke, I.D., Simpson, J.L., & van der Poel, S. (2017). The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod, 32, 1786-1801.
  • Zembayashi, M., Nishimura, K., Lunt, D.K., & Smith, S.B. (1995). Effect of breed type and sex on the fatty acid composition of subcutaneous and intramuscular lipids of finishing steers and heifers. J Anim Sci, 73, 3325-32.
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J.M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425-32.
  • Zieba, D.A., Amstalden, M., Maciel, M.N., Keisler, D.H., Raver, N., Gertler, A., & Williams, G.L. (2003). Divergent effects of leptin on luteinizing hormone and insulin secretion are dose dependent. Exp Biol Med (Maywood), 228, 325-30.
  • Zorn, B., Osredkar, J., Meden-Vrtovec, H., & Majdic, G. (2007). Leptin levels in infertile male patients are correlated with inhibin B, testosterone and SHBG but not with sperm characteristics. Int J Androl, 30, 439-44.

Effect of Leptins in Reproduction

Year 2024, Volume: 9 Issue: 1, 98 - 114, 30.04.2024

Oya Korkmaz , Ömer Faruk Karaşör , Ali Soleimanzadeh , Mustafa Numan Bucak , Sadık Küçükgünay , Mustafa Kul

https://doi.org/10.51754/cusbed.1459267

Abstract

Adipose tissue functions both as an energy store and as an active endocrine organ secreting a large number of biologically important molecules called adipokines. Adipokines have been shown to be involved in the regulation of reproductive function and the first adipokine identified was leptin. Recent research shows that leptin is not only an adipocyte-derived precursor of the amount of energy stores going to the brain, but also a hormone/cytokine crucial for a number of different physiological processes such as inflammation, angiogenesis, hematopoiesis, immune function and reproduction. Leptin, an adipocyte-derived hormone, plays an important role in numerous physiological and metabolic functions in the body, especially during puberty and reproduction. Besides its central hypothalamic effects, leptin acts in many peripheral organs (stomach, skeletal muscle, pituitary cells, placenta), including the testes, and has a regulatory role in both male reproductive and female reproductive function. Leptin is essential for normal reproductive function, but in excess it can have detrimental effects on the reproductive system. Infertile men with disorders affecting the testicular parenchyma, including non-obstructive azoospermia, oligozoospermia and oligo-astheno-teratozoospermia, are known to have high leptin concentrations. Recent studies in the literature suggest a strong association between the hypothalamic-hypophyseal-gonadal (HPG) axis, androgen regulation and sperm production, leptin and infertility. Based on these studies, it is possible to suggest that leptin excess, deficiency or resistance may be associated with abnormal reproductive function. Furthermore, these abnormalities caused by high leptin have also been associated with increased oxidative stress. If the relationship between leptin and reproduction can be fully understood, it may shed light on future targeted therapies for both male and female infertility. This review focuses on the relationship between leptin and fertility.

Keywords

Reproduction Hypothalamic-hypophyseal-gonadal axis Infertility Leptin

References

  • Abbasihormozi, S., Shahverdi, A., Kouhkan, A., Cheraghi, J., Akhlaghi, A.A., & Kheimeh, A. (2013). Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat. Arch Gynecol Obstet, 287, 1241-9.
  • Abir, R., Ao, A., Jin, S., Barnett, M., Raanani, H., Ben-Haroush, A., & Fisch, B. (2005) Leptin and its receptors in human fetal and adult ovaries. Fertil Steril, 84, 1779-82.
  • Achache, H., & Revel, A. (2006) Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update, 12, 731-46.
  • Adam, C.L., Archer, Z.A., & Miller, D.W. (2003). Leptin actions on the reproductive neuroendocrine axis in sheep. Reprod Suppl, 61, 283-97.
  • Adam, C.L., Findlay, P.A., & Miller, D.W. (2006). Blood-brain leptin transport and appetite and reproductive neuroendocrine responses to intracerebroventricular leptin injection in sheep: influence of photoperiod. Endocrinology, 147, 4589-98.
  • Agarwal, A., Ikemoto, I., & Loughlin, K.R. (1994). Relationship of sperm parameters with levels of reactive oxygen species in semen specimens. J Urol, 152, 107-10.
  • Agarwal, A., Prabakaran, S.A., & Said, T.M. (2005). Prevention of oxidative stress injury to sperm. J Androl, 26, 654-60.
  • Agarwal, A., & Saleh, R.A. (2002). Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am, 29, 817-27.
  • Agarwal SK, Vogel K, Weitsman SR, Magoffin DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab. 1999;84:1072-6.
  • Ahima, R.S., Dushay, J., Flier, S.N., Prabakaran, D., & Flier, J.S. (1997). Leptin accelerates the onset of puberty in normal female mice. J Clin Invest, 99, 391-5.
  • Ahima, R.S., & Flier, J.S. Leptin. (2000). Annu Rev Physiol, 62, 413-37.
  • Aiston, S., & Agius, L. (1999). Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin. Diabetes, 48, 15-20.
  • Aitken, R.J., Smith, T.B., Jobling, M.S., Baker, M.A., & De Iuliis, G.N. (2014). Oxidative stress and male reproductive health. Asian J Androl, 16, 31-8.
  • Almabhouh, F.A., Osman, K., Ibrahim, S.F., Gupalo, S., Gnanou, J., Ibrahim, E., & Singh, H.J. (2017). Melatonin ameliorates the adverse effects of leptin on sperm. Asian J Androl, 19, 647-654.
  • Almabhouh, F.A., Osman, K., Siti Fatimah, I., Sergey, G., Gnanou, J., & Singh, H.J. (2015). Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period. Andrologia, 47, 751-8.
  • Almabhouh, F.A., & Singh, H.J. (2023). The impact of leptin on sperm. Reprod Fertil Dev, 35(8), 459-468.
  • Almog, B., Gold, R., Tajima, K., Dantes, A., Salim, K., Rubinstein, M., Barkan, D., Homburg, R., Lessing, J.B., Nevo, N., Gertler, A., & Amsterdam, A. (2001). Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats. Mol Cell Endocrinol, 183, 179-91.
  • Amstalden, M., Garcia, M.R., Stanko, R.L., Nizielski, S.E., Morrison, C.D., Keisler, D.H., & Williams, G.L. (2002). Central infusion of recombinant ovine leptin normalizes plasma insulin and stimulates a novel hypersecretion of luteinizing hormone after short-term fasting in mature beef cows. Biol Reprod, 66, 1555-61.
  • Amstalden, M., Garcia, M.R., Williams, S.W., Stanko, R.L., Nizielski, S.E., Morrison, C.D., Keisler, D.H., & Williams, G.L. (2000). Leptin gene expression, circulating leptin, and luteinizing hormone pulsatility are acutely responsive to short-term fasting in prepubertal heifers: relationships to circulating insulin and insulin-like growth factor I(1). Biol Reprod, 63, 127-33.
  • Andrews, J.F. (1998). Leptin: energy regulation and beyond to a hormone with pan-physiological function. Proc Nutr Soc, 57, 409-11.
  • Angelopoulou, R., & Kyriazoglou, M. (2005). Sperm oxidative damage and the role of reactive oxygen species in male infertility. Arch Hell Med, 22,433-46.
  • Aquila, S., Gentile, M., Middea, E., Catalano, S., & Andò, S. (2005). Autocrine regulation of insulin secretion in human ejaculated spermatozoa. Endocrinology, 146, 552-7.
  • Aquila, S., Gentile, M., Middea, E., Catalano, S., Morelli, C., Pezzi, V., & Andò, S. (2005). Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab, 90, 4753-61.
  • Arias-Alvarez, M., Bermejo-Alvarez, P., Gutierrez-Adan, A., Rizos, D., Lorenzo, P.L., & Lonergan, P. (2011). Effect of leptin supplementation during in vitro oocyte maturation and embryo culture on bovine embryo development and gene expression patterns. Theriogenology, 75, 887-96.
  • Ashworth, C.J., Hoggard, N., Thomas, L., Mercer, J.G., Wallace, J.M., & Lea, R.G. (2000). Placental leptin. Rev Reprod, 5, 18-24.
  • Aziz, N., Saleh, R.A., Sharma, R.K., Lewis-Jones, I., Esfandiari, N., Thomas, A.J.Jr., & Agarwal, A. (2004). Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril, 81, 349-54.
  • Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J.P., Bortoluzzi, M.N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand-Brustel, Y., & Lewin, M.J. (1998). The stomach is a source of leptin. Nature, 394, 790-3.
  • Barash, I.A., Cheung, C.C., Weigle, D.S., Ren, H., Kabigting, E.B., Kuijper, J.L., Clifton, D.K., & Steiner, R.A. (1996). Leptin is a metabolic signal to the reproductive system. Endocrinology, 137, 3144-7.
  • Barb, C.R., Barrett, J.B., Kraeling, R.R., & Rampacek, G.B. (1999). Role of leptin in modulating neuroendocrine function: a metabolic link between the brain-pituitary and adipose tissue. Reprod Domest Anim, 34, 111-26.
  • Batra, A., Okur, B., Glauben, R., Erben, U., Ihbe, J., Stroh, T., Fedke, I., Chang, H.D., Zeitz, M., & Siegmund, B. (2010). Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology, 151, 56-62.
  • Bellmann, O., Wegner, J., Teuscher, F., Schneider, F., & Ender, K. (2004). Growth differences and corresponding hormone concentrations in different metabolic type of cattle. Livestock Produc Sci, 85,45-57.
  • Bernabucci, U., Basiricò, L., Lacetera, N., Morera, P., Ronchi, B., Accorsi, P.A., Seren, E., & Nardone, A. (2006). Photoperiod affects gene expression of leptin and leptin receptors in adipose tissue from lactating dairy cows. J Dairy Sci, 89, 4678-86.
  • Bertoni, L., Ferretti, M., Cavani, F., Zavatti, M., Resca, E., Benelli, A., & Palumbo, C. (2009). Leptin increases growth of primary ossification centers in fetal mice. J Anat, 215, 577-83.
  • Bjørbaek, C., Uotani, S., Da Silva, B., & Flier, J.S. (1997). Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem, 272, 32686-95.
  • Blanca, A.J., Ruiz-Armenta, M.V., Zambrano, S., Salsoso, R., Miguel-Carrasco, J.L., Fortuño, A., Revilla, E., Mate, A., & Vázquez, C.M. (2016). Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine. J Cell Biochem, 117, 2281-8.
  • Boden, G., Chen, X., Mozzoli, M., & Ryan, I. (1996). Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab, 81, 3419-23.
  • Boelhauve, M., Sinowatz, F., Wolf, E., & Paula-Lopes, F.F. (2005). Maturation of bovine oocytes in the presence of leptin improves development and reduces apoptosis of in vitro-produced blastocysts. Biol Reprod, 73, 737-44.
  • Bouloumié, A., Drexler, H.C., Lafontan, M., & Busse, R. (1998). Leptin, the product of Ob gene, promotes angiogenesis. Circ Res, 83, 1059-66.
  • Brandão, C.M., Lombardi, M.T., Nishida, S.K., Hauache, O.M., & Vieira, J.G. (2003). Serum leptin concentration during puberty in healthy nonobese adolescents. Braz J Med Biol Res, 36, 1293-6.
  • Brannian, J.D., Zhao, Y., & McElroy, M. (1999). Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action. Hum Reprod, 14, 1445-8.
  • Bray, G.A. (1997). Obesity and reproduction. Hum Reprod, 12, 26-32.
  • Brito, L., Barth, A., Rawlings, N., Wilde, R., Crews, D.Jr., Mir, P., & Kastelic, J. (2007). Circulating metabolic hormones during the peripubertal period and their association with testicular development in bulls. Reprod Domest Anim, 42, 502-8.
  • Caldefie-Chezet, F., Poulin, A., Tridon, A., Sion, B., & Vasson, M.P. (2001). Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J Leukoc Biol, 69, 414-8.
  • Camiña, J.P., Lage, M., Menendez, C., Graña, M., García-Devesa, J., Dieguez, C., & Casanueva, F.F. (2002). Evidence of free leptin in human seminal plasma. Endocrine, 17, 169-74.
  • Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., & Burn, P. (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science, 269, 546-9.
  • Caprio, M., Fabbrini, E., Isidori, A.M., Aversa, A., & Fabbri, A. (2001). Leptin in reproduction. Trends Endocrinol Metab, 12, 65-72.
  • Caprio, M., Fabbrini, E., Ricci, G., Basciani, S., Gnessi, L., Arizzi, M., Carta, A.R., De Martino, M.U., Isidori, A.M., Frajese, G.V., & Fabbri, A. (2003). Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod, 68, 1199-207.
  • Caprio, M., Isidori, A.M., Carta, A.R., Moretti, C., Dufau, M.L., & Fabbri, A. (1999). Expression of functional leptin receptors in rodent Leydig cells. Endocrinology, 140, 4939-47.
  • Cervero, A., Horcajadas, J.A., Domínguez, F., Pellicer, A., & Simón, C. (2005). Leptin system in embryo development and implantation: a protein in search of a function. Reprod Biomed Online, 10, 217-23.
  • Chavarro, J.E., Toth, T.L., Wright, D.L., Meeker, J.D., & Hauser, R. (2010). Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril, 93, 2222-31.
  • Chehab, F.F., Lim, M.E., & Lu, R. (1996). Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet, 12, 318-20.
  • Chehab, F.F., Mounzih, K., Lu, R., & Lim, M.E. (1997). Early onset of reproductive function in normal female mice treated with leptin. Science, 275, 88-90.
  • Chelikani, P.K., Ambrose, J.D., Keisler, D.H., & Kennelly, J.J. (2004). Effect of short-term fasting on plasma concentrations of leptin and other hormones and metabolites in dairy cattle. Domest Anim Endocrinol, 26, 33-48.
  • Chen, H., Charlat, O., Tartaglia, L.A., Woolf, E.A., Weng, X., Ellis, S.J., Lakey, N.D., Culpepper, J., Moore, K.J., Breitbart, R.E., Duyk, G.M., Tepper, R.I., & Morgenstern, J.P. (1996). Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell, 84, 491-5.
  • Cheung, C.C., Thornton, J.E., Nurani, S.D., Clifton, D.K., & Steiner, R.A. (2001). A reassessment of leptin's role in triggering the onset of puberty in the rat and mouse. Neuroendocrinology, 74, 12-21.
  • Chilliard, Y., Bonnet, M., Delavaud, C., Faulconnier, Y., Leroux, C., Djiane, J., & Bocquier, F. (2001). Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration. Domest Anim Endocrinol, 21, 271-95.
  • Cioffi, J.A., Van Blerkom, J., Antczak, M., Shafer, A., Wittmer, S., & Snodgrass, H.R. (1997). The expression of leptin and its receptors in pre-ovulatory human follicles. Mol Hum Reprod, 3, 467-72.
  • Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.M., Basdevant, A., Bougnères, P., Lebouc, Y., Froguel, P., & Guy-Grand, B. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature, 392, 398-401.
  • Cowley, M.A., Smart, J.L., Rubinstein, M., Cerdán, M.G., Diano, S., Horvath, T.L., Cone, R.D., & Low, M.J. (2001). Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature, 411, 480-4.
  • Craig, J.A., Zhu, H., Dyce, P.W., Wen, L., & Li, J. (2005). Leptin enhances porcine preimplantation embryo development in vitro. Mol Cell Endocrinol, 229, 141-7.
  • Cunningham, M.J., Clifton, D.K., & Steiner, R.A. (1999). Leptin's actions on the reproductive axis: perspectives and mechanisms. Biol Reprod, 60, 216-22.
  • Dayi, A., Bediz, C.S., Musal, B., Yilmaz, O., Comlekci, A., Celiloglu, M., & Cimrin, D. (2005).Comparison of leptin levels in serum and follicular fluid during the oestrous cycle in cows. Acta Vet Hung, 53, 457-67. De Ambrogi, M., Spinaci, M., Galeati, G., & Tamanini, C. (2007). Leptin receptor in boar spermatozoa. Int J Androl, 30, 458-61.
  • De Lamirande, E., & Gagnon, C. (1995). Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod.;10:15-21.
  • Doğrutekin, D., Çetin, M., & Udum, C.D. (2008). Relations between leptin and testosterone and glucose concentrations, fattening performance and reproductive development in growing bulls. J Biol Environ Sci, 2.
  • Dorn, C., Reinsberg, J., Kupka, M., Van der Ven, H., & Schild, R.L. (2003). Leptin, VEGF, IGF-1, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization. Arch Gynecol Obstet, 268, 187-93.
  • Dos Santos, E., Serazin, V., Morvan, C., Torre, A., Wainer, R., de Mazancourt, P., & Dieudonné, M.N. (2012). Adiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril, 97, 771-8.e1.
  • Duggal, P.S., Van Der Hoek, K.H., Milner, C.R., Ryan, N.K., Armstrong, D.T., Magoffin, D.A., & Norman, R.J. (2000). The in vivo and in vitro effects of exogenous leptin on ovulation in the rat. Endocrinology, 141, 1971-6.
  • Dundar, N.O., Anal, O., Dundar, B., Ozkan, H., Caliskan, S., & Büyükgebiz, A. (2005). Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants. J Pediatr Endocrinol Metab, 18, 181-7.
  • Dyer, C.J., Simmons, J.M., Matteri, R.L., & Keisler, D.H. (1997). Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well-fed and feed-restricted ewes. Domest Anim Endocrinol, 14, 119-28.
  • Ebihara, K., Ogawa, Y., Isse, N., Mori, K., Tamura, N., Masuzaki, H., Kohno, K., Yura, S., Hosoda, K., Sagawa, N., & Nakao, K. (1997). Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription. Biochem Biophys Res Commun, 241, 658-63.
  • Ehrhardt, R.A., Slepetis, R.M., Bell, A.W., & Boisclair, Y.R. (2001). Maternal leptin is elevated during pregnancy in sheep. Domest Anim Endocrinol, 21, 85-96.
  • Ehrhardt, R.A., Slepetis, R.M., Siegal-Willott, J., Van Amburgh, M.E., Bell, A.W., & Boisclair, Y.R. (2000). Development of a specific radioimmunoassay to measure physiological changes of circulating leptin in cattle and sheep. J Endocrinol, 166, 519-28.
  • El-Badry, D.A., Gamal, A., & El-Maaty, A.M.A. (2016). Seminal plasma hormonal profile of Arabian stallions that are classified ‘good’or ‘poor’for semen freezing. Asian Pac J Reprod, 5,453-8.
  • Escobar-Morreale, H.F., Escobar del Rey, F., & Morreale de Escobar, G. (1997). Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology, 138, 4485-8.
  • Farooqi, I.S., Jebb, S.A, Langmack, G., Lawrence, E., Cheetham, C.H., Prentice, A.M., Hughes, I.A., McCamish, M.A., & O'Rahilly, S. (1999). Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med, 341, 879-84.
  • Fei, H., Okano, H.J., Li, C., Lee, G.H., Zhao, C., Darnell, R., & Friedman, J.M. (1997). Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci U S A, 94, 7001-5.
  • Fejes, I., Koloszár, S., Závaczki, Z., Daru, J., Szöllösi, J., & Pál, A. (2006). Effect of body weight on testosterone/estradiol ratio in oligozoospermic patients. Arch Androl, 52, 97-102.
  • Fernandez, C.D., Fernandes, G.S., Favareto, A.P., Perobelli, J.E., Sanabria, M., & Kempinas, W.D. (2017). Decreased Implantation Numbceer After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure. Reprod Sci, 24, 234-241.
  • Florkowski, C.M., Collier, G.R., Zimmet, P.Z., Livesey, J.H., Espiner, E.A., & Donald, R.A. (1996). Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol (Oxf), 45, 769-73.
  • Fontoura, P., Mello, M.D., Gallo-Sá, P., Erthal-Martins, M.C., Cardoso, M.C., & Ramos, C. (2017). Leptin Improves Sperm Cryopreservation via Antioxidant Defense. J Reprod Infertil, 18, 172-8.
  • Fortuño, A., Bidegain, J., Baltanás, A., Moreno, M.U., Montero, L., Landecho, M.F., Beloqui, O., Díez, J., & Zalba, G. (2010). Is leptin involved in phagocytic NADPH oxidase overactivity in obesity? Potential clinical implications. J Hypertens, 28, 1944-50.
  • Frederich, R.C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B.B., & Flier, J.S. (1995). Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med, 1, 1311-4.
  • Frühbeck, G. (2006). Intracellular signalling pathways activated by leptin. Biochem J, 393, 7-20.
  • Gainsford, T., Willson, T.A., Metcalf, D., Handman, E., McFarlane, C., Ng, A., Nicola, N.A., Alexander, W.S., & Hilton, D.J. (1996). Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A, 93, 14564-8.
  • Gao, Y., Zhao, G., Song, Y., Haire, A., Yang, A., Zhao, X., & Wusiman, A. (2022). Presence of leptin and its receptor in the ram reproductive system and in vitro effect of leptin on sperm quality. PeerJ, 26, 10, e13982.
  • Garcia, M.R., Amstalden, M., Williams, S.W., Stanko, R.L., Morrison, C.D., Keisler, D.H., Nizielski, S.E., & Williams, G.L. (2002). Serum leptin and its adipose gene expression during pubertal development, the estrous cycle, and different seasons in cattle. J Anim Sci, 80, 2158-67.
  • Garcia-Mayor, R.V., Andrade, M.A., Rios, M., Lage, M., Dieguez, C., & Casanueva, F.F. (1997). Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab, 82, 2849-55.
  • Gentry, G.T.Jr., Gentry, L.R., & Godke, R.A. (2013). The effect of exogenous follicle stimulating hormone (FSH) and endogenous plasma leptin concentrations on the pregnancy rate of beef heifers subjected to fixed-timed artificial insemination (FTAI). Anim Reprod Sci, 138, 49-54.
  • Glander, H.J., Lammert, A., Paasch, U., Glasow, A., & Kratzsch, J. (2002). Leptin exists in tubuli seminiferi and in seminal plasma. Andrologia, 34, 227-33.
  • Gogga, P., Karbowska, J., Meissner, W., & Kochan, Z. (2011). Rola leptyny w regulacji metabolizmu lipidów i węglowodanów [Role of leptin in the regulation of lipid and carbohydrate metabolism]. Postepy Hig Med Dosw (Online), 65, 255-62.
  • Gong, Y., Luo, Z., Zhu, Q.L., Zheng, J.L., Tan, X.Y., Chen, Q.L., Lin, Y.C., & Lu, R.H. (2013). Characterization and tissue distribution of leptin, leptin receptor and leptin receptor overlapping transcript genes in yellow catfish Pelteobagrus fulvidraco. Gen Comp Endocrinol, 182, 1-6.
  • Gonnelli, S., Caffarelli, C., & Nuti, R. (2014). Obesity and fracture risk. Clin Cases Miner Bone Metab, 11, 9-14. González, R.R., Caballero-Campo, P., Jasper, M., Mercader, A., Devoto, L., Pellicer, A., & Simon, C. (2000). Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst. J Clin Endocrinol Metab, 85, 4883-8.
  • Gorska, E., Popko, K., Stelmaszczyk-Emmel, A., Ciepiela, O., Kucharska, A., & Wasik, M. (2010). Leptin receptors. Eur J Med Res, 15, 50-4.
  • Goumenou, A.G., Matalliotakis, I.M., Koumantakis, G.E., & Panidis, D.K. (2003). The role of leptin in fertility. Eur J Obstet Gynecol Reprod Biol, 106, 118-24.
  • Grauz, N.M., Laluoi, M., Perroz, D.D., Raposinho, P.D., Blum, W.F., & Aubert, M.L. (1998). Failure of leptin administration to advance sexual maturation in the female rat. In Proceedings of the 80th Meeting of the Endo Soc., New Orleans, Louisiana.
  • Green, E.D., Maffei, M., Braden, V.V., Proenca, R., DeSilva, U., Zhang, Y., Chua, S.C.Jr., Leibel, R.L., Weissenbach, J., & Friedman, J.M. (1995). The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7. Genome Res, 5:5-12.
  • Grumbach, M.M., & Styne. D.M. (1998). Puberty: ontogeny, neuroendocrinology, physiology, and disorders. Williams textbook of endocrinology, 9, e1625.
  • Gualillo, O., Lago. F., García, M., Menéndez, C., Señarís. R., Casanueva, F.F., & Diéguez, C. (1999). Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology, 140, 5149-53.
  • Guerra, B., Santana, A., Fuentes, T., Delgado-Guerra, S., Cabrera-Socorro, A., Dorado, C., & Calbet, J.A. (2007). Leptin receptors in human skeletal muscle. J Appl Physiol (1985), 102, 1786-92.
  • Halaas, J.L., Gajiwala, K.S., Maffei, M., Cohen, S.L., Chait, B.T., Rabinowitz, D., Lallone, R.L., Burley, S.K., & Friedman, J.M. (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269, 543-6.
  • Hamada, A., Esteves, S.C., & Agarwal, A. (2011). Unexplained male infertility: potential causes and management. Hum Androl, 1, 2-16.
  • Hamann, A., & Matthaei, S. (1996). Regulation of energy balance by leptin. Exp Clin Endocrinol Diabetes, 104, 293-300.
  • Hammoud, A.O., Gibson, M., Peterson, C.M., Meikle, A.W., & Carrell, D.T. (2008). Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril, 90, 897-904.
  • Hardie, L., Trayhurn, P., Abramovich, D., & Fowler, P. (1997). Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol (Oxf), 47, 101-6.
  • Haron, M.N., D'Souza, U.J., Jaafar, H., Zakaria, R., & Singh, H.J. (2010). Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats. Fertil Steril, 93, 322-4.
  • Hauguel-de Mouzon, S., Lepercq, J., & Catalano, P. (2006). The known and unknown of leptin in pregnancy. Am J Obstet Gynecol, 194, 1537-45.
  • Henson, M.C., & Castracane, V.D. (2006). Leptin in pregnancy: an update. Biol Reprod, 74, 218-29.
  • Henson, M.C., & Castracane, V.D. (2000). Leptin in pregnancy. Biol Reprod, 63, 1219-28.
  • Herrid, M., Palanisamy, S.K., Ciller, U.A., Fan, R., Moens, P., Smart, N.A., & McFarlane, J.R. (2014). An updated view of leptin on implantation and pregnancy: a review. Physiol Res, 63, 543-57.
  • Highman, T.J., Friedman, J.E., Huston, L.P., Wong, W.W., & Catalano, P.M. (1998). Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. Am J Obstet Gynecol, 178, 1010-5.
  • Hofny, E.R., Ali, M.E., Abdel-Hafez, H.Z., Kamal, Eel-D., Mohamed, E.E., Abd El-Azeem, H.G., & Mostafa, T. (2010). Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril, 94, 581-4.
  • Hoggard, N., Mercer, J.G., Rayner, D.V., Moar, K., Trayhurn, P., & Williams, L.M. (1997). Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem Biophys Res Commun, 232, 383-7.
  • Holness, M.J., Munns, M.J., & Sugden, M.C. (1999). Current concepts concerning the role of leptin in reproductive function. Mol Cell Endocrinol, 157, 11-20.
  • Houseknecht, K.L., Baile, C.A., Matteri, R.L., & Spurlock, M.E. (1998). The biology of leptin: a review. J Anim Sci, 76, 1405-20.
  • Houseknecht, K.L., & Portocarrero, C.P. (1998). Leptin and its receptors: regulators of whole-body energy homeostasis. Domest Anim Endocrinol, 15, 457-75.
  • Idelevich, A., Sato, K., & Baron, R. (2013). What are the effects of leptin on bone and where are they exerted? J Bone Miner Res, 28, 18-21.
  • Iikuni, N., Lam, Q.L., Lu, L., Matarese, G., & La Cava, A. (2008). Leptin and Inflammation. Curr Immunol Rev, 4, 70-79.
  • Iqbal, J., Pompolo, S., Murakami, T., Grouzmann, E., Sakurai, T., Meister, B., & Clarke, I.J. (2001). Immunohistochemical characterization of localization of long-form leptin receptor (OB-Rb) in neurochemically defined cells in the ovine hypothalamus. Brain Res, 920, 55-64.
  • Ishikawa, T., Fujioka, H., Ishimura, T., Takenaka, A., & Fujisawa, M. (2007). Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia, 39, 22-7. Isidori, A.M., Caprio, M., Strollo, F., Moretti, C., Frajese, G., Isidori, A., & Fabbri, A. (1999). Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab, 84, 3673-80.
  • Jahan, S., Bibi, R., Ahmed, S., & Kafeel, S. (2011). Leptin levels in infertile males. J Coll Physicians Surg Pak, 21, 393-7.
  • Jensen, T.K., Andersson, A.M., Jørgensen, N., Andersen, A.G., Carlsen, E., Petersen, J.H., & Skakkebaek, N.E. (2004). Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril, 82, 863-70.
  • Jia, Z., Zhang, J., Wu, Z., & Tian, J. (2012). Leptin enhances maturation and development of calf oocytes in vitro. Reprod Domest Anim, 47, 718-23.
  • Jin, L., Burguera, B.G., Couce, M.E., Scheithauer, B.W., Lamsan, J., Eberhardt, N.L., Kulig, E., & Lloyd, R.V. (1999). Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab, 84, 2903-11.
  • Johnson, L., Thompson, D.L.Jr., & Varner, D.D. (2008). Role of Sertoli cell number and function on regulation of spermatogenesis. Anim Reprod Sci, 105, 23-51.
  • Jope, T., Lammert, A., Kratzsch, J., Paasch, U., & Glander, H.J. (2003). Leptin and leptin receptor in human seminal plasma and in human spermatozoa. Int J Androl, 26, 335-41.
  • Jung, C.H., & Kim, M.S. (2013). Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res, 36, 201-7.
  • Karlsson, C., Lindell, K., Svensson, E., Bergh, C., Lind, P., Billig, H., Carlsson, L.M., & Carlsson, B. (1997). Expression of functional leptin receptors in the human ovary. J Clin Endocrinol Metab, 82, 4144-8.
  • Kemal Duru, N., Morshedi, M., & Oehninger, S. (2000). Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril, 74, 1200-7.
  • Khaki, A., Batavani, R.A., & Najafi, G. (2013). The in vitro effect of leptin on semen quality of water buffalo (Bubalus bubalis) bulls. Vet Res Forum, 4:7-12.
  • Kieffer, T.J., Heller, R.S., & Habener, J.F. (1996). Leptin receptors expressed on pancreatic beta-cells. Biochem Biophys Res Commun, 224, 522-7.
  • Kieffer, T.J., Heller, R.S., Leech, C.A., Holz, G.G., & Habener, J.F. (1997). Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes, 46, 1087-93.
  • Kiess, W., Blum, W.F., & Aubert, M.L. (1998). Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. Eur J Endocrinol, 138, 26-9.
  • Kitawaki, J., Koshiba, H., Ishihara, H., Kusuki, I., Tsukamoto, K., & Honjo, H. (2000). Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle. J Clin Endocrinol Metab, 85, 1946-50.
  • Kokkonen, T., Taponen, J., Anttila, T., Syrjälä-Qvist, L., Delavaud, C., Chilliard, Y., Tuori, M., & Tesfa, A.T. (2005). Effect of body fatness and glucogenic supplement on lipid and protein mobilization and plasma leptin in dairy cows. J Dairy Sci, 88, 1127-41.
  • Kolaczynski, J.W., Ohannesian, J.P., Considine, R.V., Marco, C.C., & Caro, J.F. (1996). Response of leptin to short-term and prolonged overfeeding in humans. J Clin Endocrinol Metab, 81, 4162-5.
  • Kort, H.I., Massey, J.B., Elsner, C.W., Mitchell-Leef, D., Shapiro, D.B., Witt, M.A., & Roudebush, W.E. (2006). Impact of body mass index values on sperm quantity and quality. J Androl, 27, 450-2.
  • Küçükkurt, İ. (2015). Leptin ve Diğer Hormonlar Üzerindeki Etkileri. Kocatepe Vet J, 8, 75-83.
  • Kulcsár, M., Dankó, G., Magdy, H.G., Reiczigel, J., Forgach, T., Proháczik, A., Delavaud, C., Magyar, K., Chilliard, Y., Solti, L., & Huszenicza, G. (2006). Pregnancy stage and number of fetuses may influence maternal plasma leptin in ewes. Acta Vet Hung, 54, 221-34.
  • Kumar, P., Saini, M., Kumar, D., Jan, M.H., Swami, D.S., & Sharma, R.K. (2016). Quantification of leptin in seminal plasma of buffalo bulls and its correlation with antioxidant status, conventional and computer-assisted sperm analysis (CASA) semen variables. Anim Reprod Sci, 166, 122-7.
  • La Cava, A., Alviggi, C., & Matarese, G. (2004). Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med (Berl), 82, 4-11.
  • Lackey, B.R., Gray, S.L., & Henricks, D.M. (2002). Measurement of leptin and insulin-like growth factor-I in seminal plasma from different species. Physiol Res, 51, 309-11.
  • Lago, R., Gómez, R., Lago, F., Gómez-Reino, J., & Gualillo, O. (2008). Leptin beyond body weight regulation--current concepts concerning its role in immune function and inflammation. Cell Immunol, 252, 139-45. Lampiao, F., & du Plessis, S.S. (2008). Insulin and leptin enhance human sperm motility, acrosome reaction and nitric oxide production. Asian J Androl, 10, 799-807.
  • Lange-Consiglio, A., Corradetti, B., Perrini, C., Bizzaro, D., & Cremonesi, F. (2016). Leptin and leptin receptor are detectable in equine spermatozoa but are not involved in in vitro fertilisation. Reprod Fertil Dev, 28, 574-85.
  • Lappas, M., Yee, K., Permezel, M., & Rice, G.E. (2005). Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies. J Endocrinol, 186, 457-65.
  • Mangian, H.F., Lee, R.G., Paul, G.L., Emmert, J.L., & Shay, N.F. (1998). Zinc deficiency suppresses plasma leptin concentrations in rats. The Journal of Nutritional Biochemistry, 9, 47-51.
  • Pradnyana, D.I.L., Pemayun, T.G., Damriyasa, I.M., & Dharmawan, N.S. (2016). Administration of leptin increases the level of Follicle Stimulating Hormone (FSH) and development of ovarian follicles in postpartum anestrus of Bali cattle. Bali Med J, 5, 69-73.
  • Reittuzzi, G., & Faggioni, R. (2000). Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol, 68, 437-46.
  • Lea, R.G., Howe, D., Hannah, L.T., Bonneau, O., Hunter, L., & Hoggard, N. (2000). Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod, 6, 763-9.
  • Lee, J.A., Kuchakulla, M., Arora, H., Kulandavelu, S., Gonzalez, E., Masterson, T.A., Hare, J.M., Kaiser, U.B., & Ramasamy, R. (2019). Age Induced Nitroso-Redox Imbalance Leads to Subclinical Hypogonadism in Male Mice. Front Endocrinol (Lausanne), 10, 190.
  • Lepercq, J., Challier, J.C., Guerre-Millo, M., Cauzac, M., Vidal, H., & Hauguel-de Mouzon, S. (2001). Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab, 86, 2409-13.
  • Li, H.W., Chiu, P.C., Cheung, M.P., Yeung, W.S., & O, W.S. (2009). Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa. Int J Androl, 32, 687-94.
  • Li, X.X., Lee, D.S., Kim, K.J., Lee, J.H., Kim, E.Y., Park, J.Y., & Kim, M.K. (2013). Leptin and nonessential amino acids enhance porcine preimplantation embryo development in vitro by intracytoplasmic sperm injection. Theriogenology, 79, 291-8.
  • Linnemann, K., Malek, A., Schneider, H., & Fusch, C. (2001). Physiological and pathological regulation of feto/placento/maternal leptin expression. Biochem Soc Trans, 29, 86-90.
  • Luukkaa, V., Pesonen, U., Huhtaniemi, I., Lehtonen, A., Tilvis, R., Tuomilehto, J., Koulu, M., & Huupponen, R. (1998). Inverse correlation between serum testosterone and leptin in men. J Clin Endocrinol Metab, 83, 3243-6.
  • Macedo, T.J.S., Santos, J.M.S., Bezerra, M.É.S., Menezes, V.G., Gouveia, B.B., Barbosa, L.M.R., Lins, T.L.B.G., Monte, A.P.O., Barberino, R.S., Batista, A.M., Barros, V.R.P., Wischral, A., Queiroz, M.A.A., Araújo, G.G.L., & Matos, M.H.T. (2019). Immunolocalization of leptin and its receptor in the sheep ovary and in vitro effect of leptin on follicular development and oocyte maturation. Mol Cell Endocrinol, 495, 110506.
  • Maciel, M.N., Zieba, D.A., Amstalden, M., Keisler, D.H., Neves, J.P., & Williams, G.L. (2004). Chronic administration of recombinant ovine leptin in growing beef heifers: effects on secretion of LH, metabolic hormones, and timing of puberty. J Anim Sci, 82, 2930-6.
  • Maciel, M.N., Zieba, D.A., Amstalden, M., Keisler, D.H., Neves, J.P., & Williams, G.L. (2004). Leptin prevents fasting-mediated reductions in pulsatile secretion of luteinizing hormone and enhances its gonadotropin-releasing hormone-mediated release in heifers. Biol Reprod, 70, 229-35.
  • Maffei, M., Halaas, J., Ravussin, E., Pratley, R.E., Lee, G.H., Zhang, Y., Fei, H., Kim, S., Lallone, R., & Ranganathan S. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med, 1, 1155-61.
  • Mahfouz, R.Z., du Plessis, S.S., Aziz, N., Sharma, R., Sabanegh, E., & Agarwal, A. (2010). Sperm viability, apoptosis, and intracellular reactive oxygen species levels in human spermatozoa before and after induction of oxidative stress. Fertil Steril, 93, 814-21.
  • Malik, N.M., Carter, N.D., Murray, J.F., Scaramuzzi, R.J., Wilson, C.A., & Stock, M.J. (2001). Leptin requirement for conception, implantation, and gestation in the mouse. Endocrinology, 142(12), 5198-202.
  • Smith, G.D., Jackson, L.M., & Foster, D.L. (2002). Leptin regulation of reproductive function and fertility. Theriogenology, 57(1), 73-86.
  • Malik, I.A., Durairajanayagam, D., & Singh, H.J. (2019). Leptin and its actions on reproduction in males. Asian J Androl, 21(3), 296-299.
  • Mangian, H.F., Lee, R.G., Paul, G.L., Emmert, J.L., & Shay, N.F. (1998). Zinc deficiency suppresses plasma leptin concentrations in rats. J Nut Biochem, 9, 47-51.
  • Mantzoros, C.S., Ozata, M., Negrao, A.B., Suchard, M.A., Ziotopoulou, M., Caglayan, S., Elashoff, R.M., Cogswell, R.J., Negro, P., Liberty, V., Wong, M.L., Veldhuis, J., Ozdemir, I.C., Gold, P.W., Flier, J.S., & Licinio, J. Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans. J Clin Endocrinol Metab. 2001, 86, 3284-91.
  • Mantzoros, C.S. (2000). Role of leptin in reproduction. Ann N Y Acad Sci, 900, 174-83.
  • Marik, P.E. Leptin, obesity, and obstructive sleep apnea. Chest. 2000;118:569-71.
  • Martins, A.D., Moreira, A.C., Sá, R., Monteiro, M.P., Sousa, M., Carvalho, R.A., Silva, B.M., Oliveira, P.F., & Alves, M.G. (2015). Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta, 1852, 1824-32.
  • Martins, F.F., Aguila, M.B., & Mandarim-de-Lacerda, C.A. (2017). Impaired steroidogenesis in the testis of leptin-deficient mice (ob/ob -/-). Acta Histochem, 119, 508-515.
  • Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Yoshimasa, Y., Tanaka, I., Mori, T., & Nakao, K. (1997). Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med, 3, 1029-33.
  • McMillen, I.C., Edwards, L.J., Duffield, J., & Muhlhausler, B.S. (2006). Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction, 131, 415-27.
  • Mercer, J.G., Moar, K.M., Findlay, P.A., Hoggard, N., & Adam, C.L. (1998). Association of leptin receptor (OB-Rb), NPY and GLP-1 gene expression in the ovine and murine brainstem. Regul Pept, 75-76, 271-8.
  • Montague, C.T., Prins, J.B., Sanders, L., Digby, J.E., & O'Rahilly, S. (1997). Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes, 46, 342-7.
  • Morrison, C.D., Daniel, J.A., Holmberg, B.J., Djiane, J., Raver, N., Gertler, A., & Keisler, D.H. (2001). Central infusion of leptin into well-fed and undernourished ewe lambs: effects on feed intake and serum concentrations of growth hormone and luteinizing hormone. J Endocrinol, 168, 317-24.
  • Mounzih, K., Lu, R., & Chehab, F.F. (1997). Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology, 138, 1190-3.
  • Mukherjea, R., Castonguay, T.W., Douglass, L.W., & Moser-Veillon, P. (1999). Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization. Life Sci, 65, 183-93.
  • Nagatani, S., Zeng, Y., Keisler, D.H., Foster, D.L., & Jaffe, C.A. (2000). Leptin regulates pulsatile luteinizing hormone and growth hormone secretion in the sheep. Endocrinology, 141, 3965-75.
  • Nikbakht, G., Mehr, M.R., Baghbanzadeh, A., Tajik, P., Tamanini, C., & Emam, M. (2010). Leptin receptor mRNA in bull ejaculated spermatozoa. Reprod Domest Anim, 45, 237-42.
  • Ogueh, O., Sooranna, S., Nicolaides, K.H., & Johnson, M.R. (2000). The relationship between leptin concentration and bone metabolism in the human fetus. J Clin Endocrinol Metab, 85, 1997-9.
  • Palmert, M.R., Radovick, S., & Boepple, P.A. (1998). The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. J Clin Endocrinol Metab, 83, 1091-6.
  • Parent, A.S., Lebrethon, M.C., Gérard, A., Vandersmissen, E., & Bourguignon, J.P. (2000). Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y. Regul Pept, 92, 17-24.
  • Paz-Filho, G., Delibasi, T., Erol, H.K., Wong, M.L., & Licinio, J. (2009). Congenital leptin deficiency and thyroid function. Thyroid Res, 2, 11.
  • Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269, 540-3.
  • Pérez-Pérez, A., Sánchez-Jiménez, F., Maymó, J., Dueñas, J.L., Varone, C., & Sánchez-Margalet, V. (2015). Role of leptin in female reproduction. Clin Chem Lab Med, 53, 15-28.
  • Rago, V., Aquila, S., Guido, C., & Carpino, A. (2009). Leptin and its receptor are expressed in the testis and in the epididymis of young and adult pigs. Anat Rec (Hoboken), 292, 736-45.
  • Reitman, M.L., Bi, S., Marcus-Samuels, B., & Gavrilova, O. (2001). Leptin and its role in pregnancy and fetal development-an overview. Biochem Soc Trans, 29, 68-72.
  • Ren, M.Q., Wegner, J., Bellmann, O., Brockmann, G.A., Schneider, F., Teuscher, F., & Ender, K. (2002). Comparing mRNA levels of genes encoding leptin, leptin receptor, and lipoprotein lipase between dairy and beef cattle. Domest Anim Endocrinol, 23, 371-81.
  • Rosenbaum, M., & Leibel, R.L. (1999). Clinical review 107: Role of gonadal steroids in the sexual dimorphisms in body composition and circulating concentrations of leptin. J Clin Endocrinol Metab, 84, 1784-9.
  • Sadock, V., Sadock, B., & Ruiz, P. (2003). Synopsis of psychiatry: behavioral sciences-clinical psychology. Translated by Rafiee H, Sobhanian K. Tehran: Arjmand Publication.
  • Sagawa, N., Yura, S., Itoh, H., Mise, H., Kakui, K., Korita, D., Takemura, M., Nuamah, M.A., Ogawa, Y., Masuzaki, H., Nakao, K., & Fujii, S. (2002). Role of leptin in pregnancy-a review. Placenta, 23, S80-6.
  • Sahu, A. (2003). Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. Front Neuroendocrinol, 24, 225-53.
  • Sáinz, N., Barrenetxe, J., Moreno-Aliaga, M.J., & Martínez, J.A. (2015). Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64, 35-46.
  • Sattar, N., Greer, I.A., Pirwani, I., Gibson, J., & Wallace, A.M. (1998). Leptin levels in pregnancy: marker for fat accumulation and mobilization? Acta Obstet Gynecol Scand, 77, 278-83.
  • Scaramuzzi, R.J., & Martin, G.B. (2008). The importance of interactions among nutrition, seasonality and socio-sexual factors in the development of hormone-free methods for controlling fertility. Reprod Domest Anim, 43, 129-36.
  • Schinzari, F., Tesauro, M., Rovella, V., Di Daniele, N., Mores, N., Veneziani, A., & Cardillo, C. (2013). Leptin stimulates both endothelin-1 and nitric oxide activity in lean subjects but not in patients with obesity-related metabolic syndrome. J Clin Endocrinol Metab, 98, 1235-41.
  • Schroeter, M.R., Leifheit-Nestler, M., Hubert, A., Schumann, B., Glückermann, R., Eschholz, N., Krüger, N., Lutz, S., Hasenfuss, G., Konstantinides, S., & Schäfer, K. (2013). Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains. Cardiovasc Res, 99, 555-65.
  • Schubring, C., Englaro, P., Siebler, T., Blum, W.F., Demirakca, T., Kratzsch, J., & Kiess, W. (1998). Longitudinal analysis of maternal serum leptin levels during pregnancy, at birth and up to six weeks after birth: relation to body mass index, skinfolds, sex steroids and umbilical cord blood leptin levels. Horm Res, 50, 276-83.
  • Schubring, C., Prohaska, F., Prohaska, A., Englaro, P., Blum, W., Siebler, T., Kratzsch, J., & Kiess, W. (1999). Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry. Eur J Obstet Gynecol Reprod Biol, 86, 151-7.
  • Sharma, K., & Considine, R.V. (1998). The Ob protein (leptin) and the kidney. Kidney Int, 53, 1483-7.
  • Shimizu, H., Shimomura, Y., Nakanishi, Y., Futawatari, T., Ohtani, K., Sato, N., & Mori, M. (1997). Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol, 154, 285-92.
  • Shiraishi, K., & Naito, K. (2007). Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol, 178, 1012-7.
  • Singh, B., Prasad, S., & Gupta, H.P. (2012). Effect of leptin on in-vitro maturation of oocytes and on early embryonic development in buffaloes. Indian J Anim Reprod, 33, 1-6.
  • Singhal, A., Farooqi, I.S., O'Rahilly, S., Cole, T.J., Fewtrell, M., & Lucas, A. (2002). Early nutrition and leptin concentrations in later life. Am J Clin Nutr, 75, 993-9.
  • Slieker, L.J., Sloop, K.W., Surface, P.L., Kriauciunas, A., LaQuier, F., Manetta, J., Bue-Valleskey, J., & Stephens, T.W. (1996). Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem, 271, 5301-4.
  • Smith, J.T., & Waddell, B.J. (2003). Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids. Endocrinology, 144, 3024-30.
  • Smith, J.T., & Waddell, B.J. (2002). Leptin receptor expression in the rat placenta: changes in ob-ra, ob-rb, and ob-re with gestational age and suppression by glucocorticoids. Biol Reprod, 67, 1204-10.
  • Sobhani, I., Bado, A., Vissuzaine, C., Buyse, M., Kermorgant, S., Laigneau, J.P., Attoub, S., Lehy, T., Henin, D., Mignon, M., & Lewin, M.J. (2000). Leptin secretion and leptin receptor in the human stomach. Gut, 47, 178-83.
  • Solinas, G. (2010). Leptin signalling coordinates lipid oxidation with thermogenesis and defence against oxidative stress. Clin Exp Pharmacol Physiol, 37, 953-4.
  • Stone, R.T., Kappes, S.M., & Beattie, C.W. (1996). The bovine homolog of the obese gene maps to chromosome 4. Mamm Genome, 7, 399-400.
  • Strobel, A., Issad, T., Camoin, L., Ozata, M., & Strosberg, A.D. (1998). A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet, 18, 213-5.
  • Sullivan, S.D., & Moenter, S.M. (2004). Gamma-aminobutyric acid neurons integrate and rapidly transmit permissive and inhibitory metabolic cues to gonadotropin-releasing hormone neurons. Endocrinology, 145, 1194-202.
  • Swain, J.E., Dunn, R.L., McConnell, D., Gonzalez-Martinez, J., & Smith, G.D. (2004). Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development. Biol Reprod, 71, 1446-52.
  • Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K.J., Smutko, J.S., Mays, G.G., Wool, E.A., Monroe, C.A., & Tepper, R.I. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell, 83, 1263-71.
  • Tena-Sempere, M., Pinilla, L., González, L.C., Diéguez, C., Casanueva, F.F., & Aguilar, E. (1999). Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol, 161, 211-8.
  • Thomas, M.G., Enns, R.M., Hallford, D.M., Keisler, D.H., Obeidat, B.S., Morrison, C.D., Hernandez, J.A., Bryant, W.D., Flores, R., Lopez, R., & Narro, L. (2002). Relationships of metabolic hormones and serum glucose to growth and reproductive development in performance-tested Angus, Brangus, and Brahman bulls. J Anim Sci, 80, 757-67.
  • Trayhurn, P., Thomas, M.E., Duncan, J.S., & Rayner, D.V. (1995). Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice. FEBS Lett, 368, 488-90.
  • Wallace, A.M. (2000). Measurement of leptin and leptin binding in the human circulation. Ann Clin Biochem, 37, 244-52.
  • Wang, Y.Y., Wang, Y.L., Li, H.P., Zhu, H.S., Jiang,.Q.D., Zhang, L., Wang, L.F., Han, L.Q., Zhong, K., Guo, Y.J., Lu, W.F., Li, H.J., & Yang, G.Y. (2011). Leptin mRNA expression in the rat mammary gland at different activation stages. Genet Mol Res, 10, 3657-63.
  • Wang, X., Zhang, X., Hu, L., & Li, H. (2018). Exogenous leptin affects sperm parameters and impairs blood testis barrier integrity in adult male mice. Reprod Biol Endocrinol, 16(1), 55.
  • Wannamethee, S.G., Shaper, A.G., Whincup, P.H., Lennon, L., & Sattar, N. (2013). Adiposity, adipokines, and risk of incident stroke in older men. Stroke, 44, 3-8.
  • Weir, C.P., & Robaire, B. (2007). Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. J Androl, 28, 229-40.
  • Wells, J.C. (2007). Sexual dimorphism of body composition. Best Pract Res Clin Endocrinol Metab, 21, 415-30. Williams, G.L., Amstalden, M., Garcia, M.R., Stanko, R.L., Nizielski, S.E., Morrison, C.D., & Keisler, D.H. (2002). Leptin and its role in the central regulation of reproduction in cattle. Domest Anim Endocrinol, 23, 339-49.
  • Wolsk, E., Mygind, H., Grøndahl, T.S., Pedersen, B.K., & van Hall, G. (2012). Human skeletal muscle releases leptin in vivo. Cytokine, 60, 667-73.
  • Yamagishi, S., Amano, S., Inagaki, Y., Okamoto, T., Takeuchi, M., & Inoue, H. (2003). Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties. Microvasc Res, 65, 186-90.
  • Yu, W.H., Kimura, M., Walczewska, A., Karanth, S., & McCann, S.M. (1997). Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci U S A, 94, 1023-8.
  • Yuan, M., Huang, G., Li, J., Zhang, J., Li, F., Li, K., Gao, B., Zeng, L., Shan, W., Lin, P., & Huang, L. (2014). Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process. Reprod Biol Endocrinol, 12, 15.
  • Zegers-Hochschild, F., Adamson, G.D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., Rienzi, L., Sunde, A., Schmidt, L., Cooke, I.D., Simpson, J.L., & van der Poel, S. (2017). The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod, 32, 1786-1801.
  • Zembayashi, M., Nishimura, K., Lunt, D.K., & Smith, S.B. (1995). Effect of breed type and sex on the fatty acid composition of subcutaneous and intramuscular lipids of finishing steers and heifers. J Anim Sci, 73, 3325-32.
  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J.M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425-32.
  • Zieba, D.A., Amstalden, M., Maciel, M.N., Keisler, D.H., Raver, N., Gertler, A., & Williams, G.L. (2003). Divergent effects of leptin on luteinizing hormone and insulin secretion are dose dependent. Exp Biol Med (Maywood), 228, 325-30.
  • Zorn, B., Osredkar, J., Meden-Vrtovec, H., & Majdic, G. (2007). Leptin levels in infertile male patients are correlated with inhibin B, testosterone and SHBG but not with sperm characteristics. Int J Androl, 30, 439-44.
There are 230 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Sciences (Other)
Journal Section Review
Authors

Oya Korkmaz 0000-0003-2923-5869

Ömer Faruk Karaşör 0000-0002-5090-779X

Ali Soleimanzadeh 0000-0002-1591-2198

Mustafa Numan Bucak 0000-0002-2955-8599

Sadık Küçükgünay 0009-0005-7520-6788

Mustafa Kul 0000-0002-9170-5094

Early Pub Date April 29, 2024
Publication Date April 30, 2024
Submission Date March 27, 2024
Acceptance Date April 24, 2024
Published in Issue Year 2024Volume: 9 Issue: 1

Cite

APA Korkmaz, O., Karaşör, Ö. F., Soleimanzadeh, A., Bucak, M. N., et al. (2024). Üremede Leptinlerin Etkisi. Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 9(1), 98-114. https://doi.org/10.51754/cusbed.1459267
 Download Cover Image

   ici2.png    logo.png        asos-index.png       crossref-logo-landscape-200.png     logo.png       search-result-logo-horizontal-TEST.jpg 

     

logo.png    scilit.jpg     goole_scholar.jpg       logo.png    logo.png


f9ab67f.png                    download