Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure
Restricted accessResearch articleFirst published online February, 2017
Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure
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 μg/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.
BellefontaineNEliasCF. Minireview: metabolic control of the reproductive physiology: Insights from genetic mouse models. Horm Behav. 2014;66(1):7–14.
2.
BellefontaineNChachlakiKParkashJVanackerC. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction. J Clin Invest. 2014;124(6):2550–2559.
3.
MessinisIEMilingosSD. Leptin in human reproduction. Hum Reprod Update. 1999;5(1):52–63.
4.
Tena-SempereMPinillaLGonzálezLCDiéguezCCasanuevaFFAguilarE. Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol. 1999;161(2):211–218.
Handjieva-DarlenskaTBoyadjievaN. The effect of high-fat diet on plasma ghrelin and leptin levels in rats. J Physiol Biochem. 2009;65(2):157–164.
7.
FernandezCDBellentaniFFFernandesGS. Diet-induced obesity in rats leads to a decrease in sperm motility. Reprod Biol Endocrinol. 2011;9:32.
8.
Aizawa-AbeMOgawaYMasuzakiH. Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest. 2000;105(9):1243–1252.
9.
Tena-SempereMBarreiroML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol. 2002;188(1-2):9–13.
10.
TeerdsKJde RooijDGKeijerJ. Functional relationship between obesity and male reproduction: from humans to animal models. Hum Reprod Update. 2011;17(5):667–683.
11.
MartinsADMoreiraACSáR. 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.
12.
NiKStegerKYangHWangHHuKChenB. Expression and role of leptin under hypoxic conditions in human testis: organotypic in vitro culture experiment and clinical study on patients with varicocele. J Urol. 2015;193(1):360–367.
13.
ChenBGuoJHLuYN. Leptin and varicocele-related spermatogenesis dysfunction: animal experiment and clinical study. Int J Androl. 2009;32(5):532–541.
14.
ChehabFFLimMELuR. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996;12(3):318–320.
15.
MounzihKLuRChehabFF. Leptin treatment rescue the sterility of genetically obese ob/ob males. Endocrinology. 1997;138(3):1190–1193.
16.
SoneMOsamuraRY. Leptin and pituitary. Pituitary. 2001;4(1-2):15–23.
17.
SchoellerELChiMDruryABertschingerAEsakkyPMoleyKH. Leptin monotherapy rescues spermatogenesis in male Akita type 1 diabetic mice. Endocrinology. 2014;155(8):2781–2786.
18.
VendraminiVCedenhoAPMiragliaSMSpaineDM. Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage. Reprod Sci. 2014;21(2):221–229.
19.
BarashIACheungCCWeigleDS. Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996;137(7):3144–3147.
20.
CunninghamMJCliftonDKSteinerRA. Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol Reprod. 1999;60(2):216–222.
21.
MagnusdottirEVThorsteinssonTThorsteinsdottirSMaria HeimisdottirMOlafsdottirK. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum Reprod. 2005;20(1):208–215.
22.
JensenTKAnderssonAMJørgensenN. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82(4):863–870.
23.
KortHIMasseyJBElsnerCW. Impact of body mass index values on sperm quantity and quality. J Androl. 2006;27(3):450–452.
24.
AlvesMGJesusTTSousaMGoldbergESilvaBMOliveiraPF. Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant?Curr Pharm Des. 2016;22(7):783–791.
25.
LandryDCloutierFMartin LucJ. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol. 2013;13(1):1–14.
26.
HaronMND’SouzaUJAJaafarHZakariaRSinghHJ. Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats. Fertil Steril. 2010;93(1):322–324.
27.
LaskeyJWKlinefelterGRKelceWREwingLL. 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.
28.
AmannRP. Use of animal models for detecting specific alterations in reproduction. Fundam Appl Toxicol. 1982;2(1):13–26.
29.
KlinefelterGR. Actions of toxicants on the structure and function of the epididymis. In: RobaireBHintonBT, eds. The Epididymis – From Molecules to Clinical Pratice. 1st ed. New York, NY: Kluwer Academic/Plenum Publisher; 2002:353–369.
30.
KlinefelterGRLaskeyJWPerreaultSD. 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.
31.
KempinasWGSuarezJDRobertsNL. Fertility of rat epididymal sperm after chemically and surgically induced sympathectomy. Biol Reprod. 1998;59(4):897–904.
32.
FernandezCDPortoEMArenaACKempinasWD. Effects of altered epididymal sperm transit time on sperm quality. Int J Androl. 2008;31(4):427–437.
33.
RobbGWAmmanRPKillianGJ. Daily sperm production and epididymal sperm reserves of puberal and adult rats. J Reprod Fertil. 1978;54(1):103–107.
34.
FernandesGSArenaACFernandezCDBMercadanteABarbisanLFKempinasWG. Reproductive effects in male rats exposed to diuron. Reprod Toxicol. 2007;23(1):106–112.
35.
IsidoriAMCaprioMStrolloF. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–3680.
36.
AbbasihormoziSShahverdiAKouhkanACheraghiJAkhlaghiAAKheimehA. 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.
37.
HanafySHalawaFAMostafaFAMikhaelNWKhalilKT. Serum leptin correlates in infertile oligozoospermic males. Andrologia. 2007;39(5):177–180.
38.
BhatGKSeaTLOlatinwoMO. 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.
39.
AggerholmASThulstrupAMToftGRamlau-HansenCHBondeJP. Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile?Fertil Steril. 2008,90(3):619–626.
40.
BakosHWMitchellMSetchellBPLaneM. 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.
41.
ChavarroJETothTLWrightDLMeekerJDHauserR. 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.
42.
Vigueras-VillaseñorRMRojas-CastañedaJCChávez-SaldañaM. Alterations in the spermatic function generated by obesity in rats. Acta Histochem. 2011;113(2):214–220.
43.
CaprioMFabbriniERicciG. Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod. 2003;68(4):1199–1207.
44.
AshbyJTinwellHLefevrePAJoinerRHasemanJ. 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.
45.
Esmaili-NejadMRBabaeiHKheirandishR. The effects of long-term leptin administration on morphometrical changes of mice testicular tissue. Iran J Basic Med Sci. 2015;18(12):1176–1182.
46.
GlanderHJLammertAPaaschUGlasowAKratzschJ. Leptin exists in tubuli seminiferi and in seminal plasma. Andrologia. 2002;34(4):227–233.
47.
ZornBOsredkarJMeden-VrtovecHMajdicG. 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.
