The role of leptin and obesity on male infertility.
Journal
Current opinion in urology
ISSN: 1473-6586
Titre abrégé: Curr Opin Urol
Pays: United States
ID NLM: 9200621
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
25
3
2020
medline:
15
12
2020
entrez:
25
3
2020
Statut:
ppublish
Résumé
Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic-pituitary-gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility. Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic-pituitary-adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology. Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.
Identifiants
pubmed: 32205811
doi: 10.1097/MOU.0000000000000762
pii: 00042307-202005000-00010
doi:
Substances chimiques
Leptin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
334-339Commentaires et corrections
Type : CommentIn
Références
Olayemi F. Review on some causes of male infertility. Afr J Biotechnol 2010; 9:
Hamada A, Esteves SC, Agarwal A. Unexplained male infertility: potential causes and management. Hum Androl 2011; 1:2–16.
Miyamoto T, Tsujimura A, Miyagawa Y, et al. Male infertility and its causes in human. Adv Urol 2012; 2012:
Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update 2014; 21:56–83.
Dohle G, Smit M, Weber R. Androgens and male fertility. World J Urol 2003; 21:341–345.
Kelly D, Jones T. Testosterone and obesity. Obes Rev 2015; 16:581–606.
Stokes VJ, Anderson RA, George JT. How does obesity affect fertility in men—and what are the treatment options? Clin Endocrinol 2015; 82:633–638.
Du Plessis SS, Cabler S, McAlister DA, et al. The effect of obesity on sperm disorders and male infertility. Nat Rev Urol 2010; 7:153–161.
Farooq R, Lutfullah S, Ahmed M. Serum leptin levels in obese infertile men and women. Pak J Pharm Sci 2014; 1:27.
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; 84:3673–3680.
Lee JA, Kuchakulla MA, Arora HM, et al. Age induced nitroso-redox imbalance leads to subclinical hypogonadism in male mice. Front Endocrinol 2019; 10:190.
Wray S. From nose to brain: development of gonadotrophin-releasing hormone-1 neurones. J Neuroendocrinol 2010; 22:743–753.
Zirkin BR, Papadopoulos V. Leydig cells: formation, function, and regulation. Biol Reprod 2018; 99:101–111.
Clavijo RI, Hsiao W. Update on male reproductive endocrinology. Transl Androl Urol 2018; 7:S367–S372.
Huhtaniemi I. A short evolutionary history of FSH-stimulated spermatogenesis. Hormones 2015; 14:468–478.
Grumbach MM, Styne DM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. Williams Textb Endocrinol 1998; 9:e1625.
Bordini B, Rosenfield RL. Normal pubertal development. Pediatr Rev 2011; 32:223.
Clayton R. Mechanism of GnRH action in gonadotrophs. Hum Reprod 1988; 3:479–483.
Jensen TK, Andersson AM, Jørgensen N, et al. Body mass index in relation to semen quality and reproductive hormones among 1558 Danish men. Fertil Steril 2004; 82:863–870.
Aggerholm AS, Thulstrup AM, Toft G, et al. Is overweight a risk factor for reduced semen quality and altered serum sex hormone profile? Fertil Steril 2008; 90:619–626.
Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27:861–868.
Strain GW, Zumoff B, Kream J, et al. Mild hypogonadotropic hypogonadism in obese men. Metabolism 1982; 31:871–875.
Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994; 79:997–1000.
Tchernof A, Després JP, Bélanger A, et al. Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism 1995; 44:513–519.
Fejes I, Koloszar S, Zavaczki Z, et al. Effect of body weight on testosterone/estradiol ratio in oligozoospermic patients. Arch Androl 2006; 52:97–102.
Hammoud AO, Gibson M, Peterson CM, et al. Obesity and male reproductive potential. J Androl 2006; 27:619–626.
Vermeulen A, Kaufman J, Giagulli V. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab 1996; 81:1821–1826.
Meachem S, Nieschlag E, Simoni M. Inhibin B in male reproduction: pathophysiology and clinical relevance. Eur J Endocrinol 2001; 145:561–571.
Pierik F, Burdorf A, de Jong F, Weber R. Inhibin B: a novel marker of spermatogenesis. Ann Med 2003; 35:12–20.
Melchor AS, Sánchez JM, Álvarez PB, et al. The impact of obesity on fertility. J Reprod Med Gynecol Obstet 2018; 3:
Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol 2018; 16:10–20.
Winters SJ, Wang C, Abdelrahaman E, et al. Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells? J Androl 2006; 27:560–564.
Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 2009; 54:1847–1856.
Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol 2008; 216:3–13.
Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc 2001; 60:329–339.
Teerds K, De Rooij D, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models. Human Reprod Update 2011; 17:667–683.
Thompson E, Patterson M, Murphy K, et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic–pituitary–gonadal axis. J Neuroendocrinol 2004; 16:850–858.
Davidson LM, Millar K, Jones C, et al. Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility. Hum Fertil 2015; 18:184–193.
Tong Q, Xu Y. Central leptin regulation of obesity and fertility. Curr Obes Rep 2012; 1:236–244.
Landry D, Cloutier F, Martin LJ. Implications of leptin in neuroendocrine regulation of male reproduction. Reprod Biol 2013; 13:1–14.
Trayhurn P. Biology of leptin: its implications and consequences for the treatment of obesity. Int J Obes 2001; 25:S26.
Stellato RK, Feldman HA, Hamdy O, et al. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care 2000; 23:490–494.
Hofny ER, Ali ME, Abdel-Hafez HZ, et al. Semen parameters and hormonal profile in obese fertile and infertile males. Fertil Steril 2010; 94:581–584.
Jope T, Lammert A, Kratzsch J, et al. Leptin and leptin receptor in human seminal plasma and in human spermatozoa. Int J Androl 2003; 26:335–341.
Hales CM, Fryar CD, Carroll MD, et al. Differences in obesity prevalence by demographic characteristics and urbanization level among adults in the United States, 2013-2016. JAMA 2018; 319:2419–2429.
Park HK, Ahima RS. Leptin signaling. F1000Prime Rep 2014; 6:73.
Berger GK, Smith-Harrison LI, Sandlow JI. Sperm agglutination: prevalence and contributory factors. Andrologia 2019; 51:e13254.
Schwartz MW, Seeley RJ, Campfield LA, et al. Identification of targets of leptin action in rat hypothalamus. J Clin Invest 1996; 98:1101–1106.
Wang Y, Kuropatwinski KK, White DW, et al. Leptin receptor action in hepatic cells. J Biol Chem 1997; 272:16216–16223.
Ghilardi N, Skoda RC. The leptin receptor activates Janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol 1997; 11:393–399.
Leonard WJ, O'Shea JJ. Jaks and STATs: biological implications. Annu Rev Immunol 1998; 16:293–322.
White DW, Kuropatwinski KK, Devos R, et al. Leptin receptor (OB-R) signaling cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 1997; 272:4065–4071.
Rodrigues AM, Suplicy HL, Radominski RB. Neuroendocrine control of food intake: implications in the genesis of obesity. Arq Bras Endocrinol Metab 2003; 47:398–409.
Luquet S, Perez FA, Hnasko TS, Palmiter RD. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 2005; 310:683–685.
Zhang ZY, Dodd GT, Tiganis T. Protein tyrosine phosphatases in hypothalamic insulin and leptin signaling. Trends Pharmacol Sci 2015; 36:661–674.
Stephens TW, Basinski M, Bristow PK, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 1995; 377:530.
Moran O, Phillip M. Leptin: obesity, diabetes and other peripheral effects: a review. Pediatr Diabetes 2003; 4:101–109.
Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348:159–161.
Gurzov EN, Stanley WJ, Pappas EG, et al. The JAK/STAT pathway in obesity and diabetes. FEBS J 2016; 283:3002–3015.
Schwartz MW, Peskind E, Raskind M, et al. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med 1996; 2:589.
Vaisse C, Halaas JL, Horvath CM, et al. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 1996; 14:95.
Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism 2015; 64:35–46.
Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol 2008; 52:1201–1210.
McPherson NO, Lane M. Male obesity and subfertility, is it really about increased adiposity? Asian J Androl 2015; 17:450.
Jahan S, Bibi R, Ahmed S, Kafeel S. Leptin levels in infertile males. J Coll Physicians Surg Pak 2011; 21:393–397.
Amjad S, Baig M, Zahid N, et al. Association between leptin, obesity, hormonal interplay and male infertility. Andrologia 2019; 51:e13147.