Abstract
Leptin is a protein secreted by the adipocytes, which serves as a link between fat and brain. Its main action is to decrease appetite and increase energy expenditure, but it is also involved in the control of different neuroendocrine systems, including gonadal axis. Although the effects of leptin deficiency on reproduction are well recognized, the effect of excess leptin on male reproductive function is not clear. The aim of this study was to evaluate fertility and sperm parameters of male rats exposed to exogenous leptin. A group of adult male rats received exogenous leptin intraperitoneally (30 mg/kg/day) for 42 days, and a control group received only the vehicle during the same period. After the treatment, animals were evaluated for sperm count, sperm motility, and fertility after intrauterine artificial insemination. There was no statistically significant difference between the groups related to sperm production, sperm concentration, and sperm motility. However, fertility evaluation after artificial insemination showed a quantitative decrease in the uterus plus fetuses weight, number of implantation sites, and number of live fetuses. The fertility potential showed a reduction of about 40%, whereas the preimplantation loss rate increased more than 2-fold in leptin-treated animals. In conclusion, leptin administration to nonobese male rats impairs ability of treated animals to generate offspring, since the occurrence of implantation was diminished. So leptin can impair sperm quality, affecting the reproductive capacity.
Similar content being viewed by others
References
Bellefontaine N, Elias CF. Minireview: metabolic control of the reproductive physiology: Insights from genetic mouse models. Horm Behav. 2014;66(1):7–14.
Bellefontaine N, Chachlaki K, Parkash J, Vanacker C, et al. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction. J Clin Invest. 2014;124(6):2550–2559.
Messinis IE, Milingos SD. Leptin in human reproduction. Hum Reprod Update. 1999;5(1):52–63.
Tena-Sempere M, Pinilla L, González LC, Diéguez C, Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol. 1999;161(2):211–218.
Auwerx J, Staels B. Leptin. Lancet. 1998;351(9104):737–742.
Handjieva-Darlenska T, Boyadjieva N. The effect of high-fat diet on plasma ghrelin and leptin levels in rats. J Physiol Biochem. 2009;65(2):157–164.
Fernandez CD, Bellentani FF, Fernandes GS, et al. Diet-induced obesity in rats leads to a decrease in sperm motility. Reprod Biol Endocrinol. 2011;9:32.
Aizawa-Abe M, Ogawa Y, Masuzaki H, et al. Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest. 2000;105(9):1243–1252.
Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol. 2002;188(1-2):9–13.
Teerds KJ, de Rooij DG, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models. Hum Reprod Update. 2011;17(5):667–683.
Martins AD, Moreira AC, Sá R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 2015;1852(9):1824–1832.
Ni K, Steger K, Yang H, Wang H, Hu K, Chen B. Expression and role of leptin under hypoxic conditions in human testis: organo-typic in vitro culture experiment and clinical study on patients with varicocele. J Urol. 2015;193(1):360–367.
Chen B, Guo JH, Lu YN, et al. Leptin and varicocele-related spermatogenesis dysfunction: animal experiment and clinical study. Int J Androl. 2009;32(5):532–541.
Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996;12(3):318–320.
Mounzih K, Lu R, Chehab FF. Leptin treatment rescue the sterility of genetically obese ob/ob males. Endocrinology. 1997;138(3):1190–1193.
Sone M, Osamura RY. Leptin and pituitary. Pituitary. 2001;4(1-2):15–23.
Schoeller EL, Chi M, Drury A, Bertschinger A, Esakky P, Moley KH. Leptin monotherapy rescues spermatogenesis in male Akita type 1 diabetic mice. Endocrinology. 2014;155(8):2781–2786.
Vendramini V, Cedenho AP, Miraglia SM, Spaine DM. Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage. Reprod Sci. 2014;21(2):221–229.
Barash IA, Cheung CC, Weigle DS, et al. Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996;137(7):3144–3147.
Cunningham MJ, Clifton DK, Steiner RA. Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol Reprod. 1999;60(2):216–222.
Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Maria Heimisdottir M, Olafsdottir K. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum Reprod. 2005;20(1):208–215.
Jensen TK, Andersson AM, Jørgensen N, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82(4):863–870.
Kort HI, Massey JB, Elsner CW, et al. Impact of body mass index values on sperm quantity and quality. J Androl. 2006;27(3):450–452.
Alves MG, Jesus TT, Sousa M, Goldberg E, Silva BM, Oliveira PF. Male fertility and obesity: are ghrelin, leptin and glucagonlike peptide-1 pharmacologically relevant? Curr Pharm Des. 2016;22(7):783–791.
Landry D, Cloutier F, Martin Luc J. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol. 2013;13(1):1–14.
Haron MN, D’Souza UJA, Jaafar H, Zakaria R, Singh HJ. Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats. Fertil Steril. 2010;93(1):322–324.
Laskey JW, Klinefelter GR, Kelce WR, Ewing LL. Effect of ethane dimethanesulphonate on adult and immature rabbit Leydig cells: comparison with EDS treated rat Leydig cells. Biol Reprod. 1994;50(5):1151–1160.
Amann RP. Use of animal models for detecting specific alterations in reproduction. Fundam Appl Toxicol. 1982;2(1):13–26.
Klinefelter GR. Actions of toxicants on the structure and function of the epididymis. In: Robaire B, Hinton BT, eds. The Epididymis - From Molecules to Clinical Pratice. 1st ed. New York, NY: Kluwer Academic/Plenum Publisher; 2002:353–369.
Klinefelter GR, Laskey JW, Perreault SD, et al. The ethane dimethanesulphonate-induced decrease in the fertilizing ability of cauda epididymal sperm is independent of the testis. J Androl. 1994, 15(4):318–327.
Kempinas WG, Suarez JD, Roberts NL, et al. Fertility of rat epididymal sperm after chemically and surgically induced sym-pathectomy. Biol Reprod. 1998;59(4):897–904.
Fernandez CD, Porto EM, Arena AC, Kempinas WD. Effects of altered epididymal sperm transit time on sperm quality. Int J Androl. 2008;31(4):427–437.
Robb GW, Amman RP, Killian GJ. Daily sperm production and epididymal sperm reserves of puberal and adult rats. J Reprod Fertil. 1978;54(1):103–107.
Fernandes GS, Arena AC, Fernandez CDB, Mercadante A, Bar-bisan LF, Kempinas WG. Reproductive effects in male rats exposed to diuron. Reprod Toxicol. 2007;23(1):106–112.
Isidori AM, Caprio M, Strollo F, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–3680.
Abbasihormozi S, Shahverdi A, Kouhkan A, Cheraghi J, Akhla-ghi AA, Kheimeh A. 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. 2013;287(6):1241–1249.
Hanafy S, Halawa FA, Mostafa FA, Mikhael NW, Khalil KT. Serum leptin correlates in infertile oligozoospermic males. Andrologia. 2007;39(5):177–180.
Bhat GK, Sea TL, Olatinwo MO, et al. Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse. J Androl. 2006;27(2):302–310.
Aggerholm AS, Thulstrup AM, Toft G, Ramlau-Hansen CH, Bonde JP. Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile? Fertil Steril. 2008,90(3): 619–626.
Bakos HW, Mitchell M, Setchell BP, Lane M. The effect of paternal diet induced obesity on sperm function and fertilization in a mouse model. Int J Androl. 2010;34(5 pt 1):402–410.
Chavarro JE, Toth TL, Wright DL, Meeker JD, Hauser R. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril. 2010, 93(7): 2222–2231.
Vigueras-Villaseñor RM, Rojas-Castañeda JC, Chávez-Saldaña M, et al. Alterations in the spermatic function generated by obesity in rats. Acta Histochem. 2011;113(2):214–220.
Caprio M, Fabbrini E, Ricci G, et al. Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod. 2003;68(4):1199–1207.
Ashby J, Tinwell H, Lefevre PA, Joiner R, Haseman J. The effect on sperm production in adult Sprague-Dawley rats exposed by gavage to bisfenol A between postnatal days 91–97. Toxicol Sci. 2003;74(1):129–138.
Esmaili-Nejad MR, Babaei H, Kheirandish R. The effects of long-term leptin administration on morphometrical changes of mice testicular tissue. Iran J Basic Med Sci. 2015;18(12):1176–1182.
Glander HJ, Lammert A, Paasch U, Glasow A, Kratzsch J. Leptin exists in tubuli seminiferi and in seminal plasma. Andrologia. 2002;34(4):227–233.
Zorn B, Osredkar J, Meden-Vrtovec H, Majdic G. Leptin levels in infertile male patients are correlated with inhibin B, testosterone and SHBG but not with sperm characteristics. Int J Androl. 2007;30(5):439–444.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fernandez, C.D.B., Fernandes, G.S.A., Favareto, A.P.A. et al. Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure. Reprod. Sci. 24, 234–241 (2017). https://doi.org/10.1177/1933719116653678
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719116653678