Leptin and Male Reproduction

doi:10.12280/gjszjk.20200499

Abstract

Abstract:

The downward trend in male fertility has become increasingly obvious in the world. To clarify the etiology and pathogenesis of this trend is very helpful for the precision treatment of male infertility. Leptin, a hormone produced mainly by adipose tissue, plays an important role in regulating energy metabolism, responding to inflammation, promoting the development of reproductive system and maintaining reproductive function. Leptin and its receptor can widely express in mammals′ HPG axis, testicular tissue, genital tract, accessory glands and sperm. The abnormal expression of leptin is related to the delayed development or dysfunction of the male reproductive system. To verify the leptin expression in male reproductive system and to elucidate its molecular mechanism may provide critical theoretical evidences for the clinical treatment of reproductive diseases such as male infertility.

Key words: Leptin, Receptors, leptin, Urogenital system, Fertility, Spermatogenesis, Hypothalamus-pituitary-gonad axis

JIN Ming-hao, HUANG Wen-yi, ZHANG Meng-yi, ZHANG Yi-wei, LIU Yue, DING Zhi-de. Leptin and Male Reproduction[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(1): 38-43.

References 40

[1]	Peelman F, Zabeau L, Moharana K, et al. 20 years of leptin: insights into signaling assemblies of the leptin receptor[J]. J Endocrinol, 2014,223(1):T9-T23. doi: 10.1530/JOE-14-0264.
[2]	Chavarro JE, Toth TL, Wright DL, et al. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic[J]. Fertil Steril, 2010,93(7):2222-2231. doi: 10.1016/j.fertnstert.2009.01.100.
[3]	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?[J]. Biochim Biophys Acta, 2015,1852(9):1824-1832. doi: 10.1016/j.bbadis.2015.06.005.
[4]	Cheraghi H, Zendehdel M, Ghiasi Ghalehkandi J, et al. The Effect of Leptin on Sex Hormones and Antioxidant Enzyme Levels in Obese and Normal Male Rats[J]. Int J Pept Res Ther, 2019,25(3):1105-1111. doi: 10.1007/s10989-018-9758-x.
[5]	王晓烔, 张晓柯, 胡廉. 脂肪因子对睾丸雄激素生成的调节作用[J]. 国际生殖健康/计划生育杂志, 2016,35(5):395-399.
[6]	甄锦壮. 精浆瘦素及IL-8水平与精液质量参数变化的相关分析[J]. 中国妇幼保健, 2015,30(35):6298-6299. doi: 10.7620/zgfybj.j.issn.1001-4411.2015.35.52.
[7]	Gorska E, Popko K, Stelmaszczyk-Emmel A, et al. Leptin receptors[J]. Eur J Med Res, 2010,15(Suppl 2):50-54. doi: 10.1186/2047-783x-15-s2-50.
[8]	Zhang Y, Chua S Jr. Leptin Function and Regulation[J]. Compr Physiol, 2017,8(1):351-369. doi: 10.1002/cphy.c160041.
[9]	La Cava A. Leptin in inflammation and autoimmunity[J]. Cytokine, 2017,98:51-58. doi: 10.1016/j.cyto.2016.10.011.
[10]	Aquila S, Gentile M, Middea E, et al. Leptin secretion by human ejaculated spermatozoa[J]. J Clin Endocrinol Metab, 2005,90(8):4753-4761. doi: 10.1210/jc.2004-2233.
[11]	Khodamoradi K, Parmar M, Khosravizadeh Z, et al. The role of leptin and obesity on male infertility[J]. Curr Opin Urol, 2020,30(3):334-339. doi: 10.1097/MOU.0000000000000762.
[12]	Yin C, Kang L, Lai C, et al. Effects of 17β-estradiol on leptin signaling in anterior pituitary of ovariectomized rats[J]. Exp Anim, 2017,66(2):159-166. doi: 10.1538/expanim.16-0087.
[13]	Wang X, Zhang X, Hu L, et al. Exogenous leptin affects sperm parameters and impairs blood testis barrier integrity in adult male mice[J]. Reprod Biol Endocrinol, 2018,16(1):55. doi: 10.1186/s12958-018-0368-4.
[14]	Almabhouh FA, Md Mokhtar AH, Malik IA, et al. Leptin and reproductive dysfunction in obese men[J]. Andrologia, 2020,52(1):e13433. doi: 10.1111/and.13433.
[15]	Vauthier V, Roujeau C, Chen P, et al. Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling[J]. Mol Metab, 2017,6(1):159-172. doi: 10.1016/j.molmet.2016.10.009.
[16]	Williams KW, Sohn JW, Donato J Jr, et al. The acute effects of leptin require PI3K signaling in the hypothalamic ventral premammillary nucleus[J]. J Neurosci, 2011,31(37):13147-13156. doi: 10.1523/JNEUROSCI.2602-11.2011.
[17]	Harter C, Kavanagh GS, Smith JT. The role of kisspeptin neurons in reproduction and metabolism[J]. J Endocrinol, 2018,238(3):R173-R183. doi: 10.1530/JOE-18-0108.
[18]	Zuure WA, Quennell JH, Anderson GM. Leptin Responsive and GABAergic Projections to the Rostral Preoptic Area in Mice[J]. J Neuroendocrinol, 2016,28(3):12357. doi: 10.1111/jne.12357.
[19]	Herrid M, O′Shea T, McFarlane JR. Ontogeny of leptin and its receptor expression in mouse testis during the postnatal period[J]. Mol Reprod Dev, 2008,75(5):874-880. doi: 10.1002/mrd.20796.
[20]	El-Hefnawy T, Ioffe S, Dym M. Expression of the leptin receptor during germ cell development in the mouse testis[J]. Endocrinology, 2000,141(7):2624-2630. doi: 10.1210/endo.141.7.7542.
[21]	Gombar FM, Ramos CF. Leptin and leptin receptor are expressed only in clear cells of rat epididymis epithelia[J]. Int J Morphol, 2017,35(4):1303-1308. doi: 10.4067/S0717-95022017000401303.
[22]	Siemińska L, Borowski A, Marek B, et al. Serum concentrations of adipokines in men with prostate cancer and benign prostate hyperplasia[J]. Endokrynol Pol, 2018,69(2):120-127. doi: 10.5603/EP.a2018.0006.
[23]	Malendowicz W, Rucinski M, Belloni AS, et al. Real-time PCR analysis of leptin and leptin receptor expression in the rat prostate, and effects of leptin on prostatic acid phosphatase release[J]. Int J Mol Med, 2006,18(6):1097-1100.
[24]	Camiña JP, Lage M, Menendez C, et al. Evidence of free leptin in human seminal plasma[J]. Endocrine, 2002,17(3):169-174. doi: 10.1385/ENDO:17:3:169.
[25]	Jope T, Lammert A, Kratzsch J, et al. Leptin and leptin receptor in human seminal plasma and in human spermatozoa[J]. Int J Androl, 2003,26(6):335-341. doi: 10.1111/j.1365-2605.2003.00434.x.
[26]	李素娟. 不同青春发育阶段儿童青少年血清leptin、Kisspeptin水平的变化[D]. 北京:北京协和医学院, 2015.
[27]	Zhai L, Zhao J, Zhu Y, et al. Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity[J]. Endocrine, 2018,62(1):195-206. doi: 10.1007/s12020-018-1646-9.
[28]	Petrine J, Franci CR, Del Bianco-Borges B. Leptin actions through the nitrergic system to modulate the hypothalamic expression of the kiss1 mRNA in the female rat[J]. Brain Res, 2020,1728:146574. doi: 10.1016/j.brainres.2019.146574.
[29]	Tsatsanis C, Dermitzaki E, Avgoustinaki P, et al. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis[J]. Hormones(Athens), 2015,14(4):549-562. doi: 10.14310/horm.2002.1649.
[30]	Donato J Jr, Cravo RM, Frazão R, et al. Hypothalamic sites of leptin action linking metabolism and reproduction[J]. Neuroendocrinology, 2011,93(1):9-18. doi: 10.1159/000322472.
[31]	周伟航, 陈少岸, 于丰浩, 等. 运动对男性生殖影响的研究进展[J]. 国际生殖健康/计划生育杂志, 2018,37(3):257-261. doi: 10.3969/j.issn.1674-1889.2018.03.019.
[32]	Del Bianco-Borges B, Franci CR. Estrogen-dependent post-translational change in the nitric oxide system may mediate the leptin action on LH and prolactin secretion[J]. Brain Res, 2015,1604:62-73. doi: 10.1016/j.brainres.2015.02.001.
[33]	Landry D, Cloutier F, Martin LJ. Implications of leptin in neuroendocrine regulation of male reproduction[J]. Reprod Biol, 2013,13(1):1-14. doi: 10.1016/j.repbio.2012.12.001.
[34]	Caprio M, Isidori AM, Carta AR, et al. Expression of functional leptin receptors in rodent Leydig cells[J]. Endocrinology, 1999,140(11):4939-4947. doi: 10.1210/endo.140.11.7088.
[35]	Glander HJ, Lammert A, Paasch U, et al. Leptin exists in tubuli seminiferi and in seminal plasma[J]. Andrologia, 2002,34(4):227-233. doi: 10.1046/j.1439-0272.2002.00501.x.
[36]	Almabhouh FA, Osman K, Ibrahim SF, et al. Melatonin ameliorates the adverse effects of leptin on sperm[J]. Asian J Androl, 2017,19(6):647-654. doi: 10.4103/1008-682X.183379.
[37]	Kwon O, Kim KW, Kim MS. Leptin signalling pathways in hypothalamic neurons[J]. Cell Mol Life Sci, 2016,73(7):1457-1477. doi: 10.1007/s00018-016-2133-1.
[38]	Md Mokhtar AH, Malik IA, Abd Aziz NAA, et al. LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats[J]. Andrologia, 2019,51(3):e13196. doi: 10.1111/and.13196.
[39]	Almabhouh FA, Singh HJ. Adverse effects of leptin on histone-to-protamine transition during spermatogenesis are prevented by melatonin in Sprague-Dawley rats[J]. Andrologia, 2018,50(1). doi: 10.1111/and.12814.
[40]	Lampiao F, du Plessis SS. Insulin and leptin enhance human sperm motility, acrosome reaction and nitric oxide production[J]. Asian J Androl, 2008,10(5):799-807. doi: 10.1111/j.1745-7262.2008.00421.x.