Skip to main content

Advertisement

Log in

Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bellefontaine N, Elias CF. Minireview: metabolic control of the reproductive physiology: Insights from genetic mouse models. Horm Behav. 2014;66(1):7–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Messinis IE, Milingos SD. Leptin in human reproduction. Hum Reprod Update. 1999;5(1):52–63.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. Auwerx J, Staels B. Leptin. Lancet. 1998;351(9104):737–742.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol Cell Endocrinol. 2002;188(1-2):9–13.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Mounzih K, Lu R, Chehab FF. Leptin treatment rescue the sterility of genetically obese ob/ob males. Endocrinology. 1997;138(3):1190–1193.

    Article  CAS  PubMed  Google Scholar 

  16. Sone M, Osamura RY. Leptin and pituitary. Pituitary. 2001;4(1-2):15–23.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Barash IA, Cheung CC, Weigle DS, et al. Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996;137(7):3144–3147.

    Article  CAS  PubMed  Google Scholar 

  20. Cunningham MJ, Clifton DK, Steiner RA. Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol Reprod. 1999;60(2):216–222.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. Landry D, Cloutier F, Martin Luc J. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol. 2013;13(1):1–14.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. Amann RP. Use of animal models for detecting specific alterations in reproduction. Fundam Appl Toxicol. 1982;2(1):13–26.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Chapter  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    CAS  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. Hanafy S, Halawa FA, Mostafa FA, Mikhael NW, Khalil KT. Serum leptin correlates in infertile oligozoospermic males. Andrologia. 2007;39(5):177–180.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. 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.

    Article  CAS  PubMed  Google Scholar 

  43. Caprio M, Fabbrini E, Ricci G, et al. Ontogenesis of leptin receptor in rat Leydig cells. Biol Reprod. 2003;68(4):1199–1207.

    Article  CAS  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    PubMed  PubMed Central  Google Scholar 

  46. 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.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carla D. B. Fernandez MSc, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116653678

Keywords

Navigation