Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort

Reproductive Biology and Endocrinology

Ralf R Henkel²  Roelof Menkveld¹  Patrick JD Bouic³  Kristian Leisegang⁴ 

[1] Department of Obstetrics and Gynaecology, Stellenbosch University & Tygerberg Academic Hospital, Parow Valley, Cape Town 7500, South Africa;Department of Medical Biosciences, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa;Division of Medical Microbiology, Department of Pathology, Stellenbosch University & Tygerberg Academic Hospital, Parow Valley, Cape Town 7500, South Africa;School of Natural Medicine, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa

关键词: Male fertility;    Glucose;    Leptin;    Insulin;    Semen;    Obesity;   

Others  :  804326
DOI  :  10.1186/1477-7827-12-34

 received in 2014-02-12, accepted in 2014-05-01,  发布年份 2014

【 摘 要 】

Background

Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated.

Methods

This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed medical history and examination, participants meeting the inclusion criteria were entered for data analysis. Body parameters such as BMI, waist and hip circumference and the waist hip ratio were measured. Serum and semen samples were collected and assayed for insulin, leptin and glucose. Semen samples also underwent a standard semen analysis, with sperm mitochondrial membrane potential (MMP) and DNA fragmentation (DF).

Results

Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology.

Conclusions

Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute to the contradictive information available in the literature on the impact of obesity and male reproduction.

【 授权许可】

   
2014 Leisegang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Haslam DW, James WP: Obesity. Lancet 2005, 366:1197-1209.
• [2]World Health Organisation: Obesity: preventing and managing the global epidemic. Geneva: WHO Technical Report Series number 894; 2000.
• [3]Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009, 120:1640-1645.
• [4]Zeyda M, Stulnig TM: Obesity, inflammation, and insulin resistance - a mini-review. Gerontology 2009, 55:379-386.
• [5]du Plessis SS, Cabler S, McAlister DA, Sabanegh E, Agarwal A: The effect of obesity on sperm disorders and male infertility. Nat Rev Urol 2010, 7:153-161.
• [6]World Health Organisation: WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th edition. 2010. [Department of Reproductive Health and Research]
• [7]Kefer JC, Agarwal A, Sabanegh E: Role of antioxidants in the treatment of male infertility. Int J Urol 2009, 16:449-457.
• [8]Aitken RJ: Sperm function tests and fertility. Int J Androl 2006, 29:69-75.
• [9]Marchetti P, Ballot C, Jouy N, Thomas P, Marchetti C: Influence of mitochondrial membrane potential of spermatozoa on in vitro fertilisation outcome. Andrologia 2012, 44:136-141.
• [10]Henkel R, Hoogendijk CF, Bouic PJ, Kruger TF: TUNEL assay and SCSA determine different aspects of sperm DNA damage. Andrologia 2010, 42:305-313.
• [11]Hamada A, Esteves SC, Nizza M, Agarwal A: Unexplained male infertility: diagnosis and management. Int Braz J Urol 2012, 38:576-594.
• [12]Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, Van Wely M, Cao J, Martini AC, Eskandar M, Chavarro JE, Koloszar S, Twigt JM, Ramlau-Hansen CH, Borges E Jr, Lotti F, Steegers-Theunissen RP, Zorn B, Polotsky AJ, La Vignera S, Eskenazi B, Tremellen K, Magnusdottir EV, Fejes I, Hercberg S, Lévy R, Czernichow S: BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update 2013, 19:221-231.
• [13]Palmer NO, Bakos HW, Fullston T, Lane M: Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2012, 1:253-263.
• [14]Hammoud AO, Gibson M, Peterson CM, Meikle W, Carrell DT: Impact of male obesity on infertility: a critical review of the current literature. Fert Steril 2008, 90:897-904.
• [15]MacDonald AA, Herbison GP, Showell M, Farquhar CM: The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 2010, 16:293-311.
• [16]Bakos HW, Henshaw RC, Mitchell M, Lane M: Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil Steril 2011, 95:1700-1704.
• [17]Lampiao F, Agarwal A, du Plessis SS: The role of insulin and leptin in male reproduction. Arch Med Sci 2009, 5:S48-S54.
• [18]Aquila S, Gentile M, Middea E, Catalano S, Andò S: Autocrine regulation of insulin secretion in human ejaculated spermatozoa. Endocrinology 2005, 146:552-557.
• [19]Aquila S, Gentile M, Middea E, Catalano S, Morelli C, Pezzi V, Andò S: Leptin secretion by human ejaculated spermatozoa. J Clin Endocrinol Metab 2005, 90:4753-4761.
• [20]Andò S, Aquila S: Arguments raised by the recent discovery that insulin and leptin are expressed in and secreted by human ejaculated spermatozoa. Mol Cell Endocrinol 2005, 245:1-6.
• [21]Lampiao F, du Plessis SS: Insulin and leptin enhance human sperm motility, acrosome reaction and nitric oxide production. Asian J Androl 2008, 10:799-807.
• [22]Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Komatsu M, Tahara H, Koyama H, Shoji T, Inaba M, Nishizawa Y: Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose. J Clin Endocrinol Metab 2004, 89:1481-1484.
• [23]Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA: The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod 1990, 5:586-592.
• [24]Politch JA, Tucker L, Bowman FP, Anderson DJ: Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007, 22:2928-2935.
• [25]Henkel R, Fransman WO, Hipler UC, Wiegand C, Schreiber G, Menkveld R, Weitz F, Fisher D: Typha capensis (Rohrb.) N.E.Br. (bulrush) extract scavenges free radicals, inhibits collagenase activity and affects human sperm motility and mitochondrial membrane potential in vitro – a pilot study. Andrologia 2012, 44(Suppl. 1):287-294.
• [26]Quinn P, Kerin JF, Warnes GM: Improved pregnancy rate in human in vitro fertilization with the use of a medium based on the composition of human tubal fluid. Fertil Steril 1985, 44:493-498.
• [27]Henkel R, Hajimohammad M, Stalf T, Hoogendijk C, Mehnert C, Menkveld R, Gips H, Schill W-B, Kruger TF: Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertil Steril 2004, 81:965-972.
• [28]Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, Lewis SE: Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online 2013, 26:68-78.
• [29]Fariello RM, Pariz JR, Spaine DM, Cedenho AP, Bertolla RP, Fraietta R: Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. BJU Int 2012, 110:863-867.
• [30]Huang PL: A comprehensive definition for metabolic syndrome. DMM 2009, 2:231-237.
• [31]Gallagher EJ, Leroith D, Karnieli E: Insulin resistance in obesity as the underlying cause for the metabolic syndrome. Mt Sinai J Med 2010, 77:511-523.
• [32]Kwon H, Pessin JE: Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 2013, 12:71.
• [33]Casabiell X, Piñeiro V, Vega F, De La Cruz LF, Diéguez C, Casanueva FF: Leptin, reproduction and sex steroids. Pituitary 2001, 4:93-99.
• [34]Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B: Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006, 17:4-12.
• [35]Hanafy S, Halawa FA, Mostafa T, Mikhael NW, Khalil KT: Serum leptin correlates in infertile oligozoospermic males. Andrologia 2007, 39:177-180.
• [36]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, 30:439-444.
• [37]Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A: Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab 2004, 6:208-215.
• [38]Zitzmann M, Erren M, Kamischke A, Simoni M, Nieschlag E: Endogenous progesterone and the exogenous progestin norethisterone enanthate are associated with a proinflammatory profile in healthy men. J Clin Endocrinol Metab 2005, 90:6603-6608.
• [39]Schoeller EL, Albanna G, Frolova AI, Moley KH: Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility. Diabetes 2012, 61:1869-1878.
• [40]Paz G, Homonnai ZT, Ayalon D, Cordova T, Kraicer PF: Immunoreactive insulin in serum and seminal plasma of diabetic and nondiabetic men and its role in the regulation of spermatozoal activity. Fertil Steril 1977, 28:836-840.
• [41]Stahler MS, Budd GC, Pansky B: Evidence for insulin synthesis in normal mouse seminal vesicle based on in situ RNA-DNA hybridization. Biol Reprod 1987, 36:999-1006.
• [42]García-Díez LC, Corrales Hernandez JJ, Hernandez-Diaz J, Pedraz MJ, Miralles JM: Semen characteristics and diabetes mellitus: significance of insulin in male infertility. Arch Androl 1991, 26:119-128.
• [43]La Vignera S, Condorelli R, Vicari E, D'Agata R, Calogero AE: Diabetes mellitus and sperm parameters. J Androl 2012, 33:145-153.
• [44]Li HW, Chiu PC, Cheung MP, Yeung WS, WS O: Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa. Int J Androl 2009, 32:687-694.
• [45]Hicks JJ, Rojas L, Rosado A: Insulin regulation of spermatozoa metabolism. Endocrinology 1973, 92:833-839.
• [46]Povoa Junior H, Rezende MTL, Souza AC: Insulina imunoreativa em líquidos biológicos. Mem Inst Oswaldo Cruz 1973, 71:425-438.
• [47]Truta Z, Garlovanu M, Lerintiu S, Micu R: A new method for human semen glucose concentration evaluation. Rom Biotech Lett 2010, 15:5764-5772.
• [48]Diamandis EP, Arnett WP, Foussias G, Pappas H, Ghandi S, Melegos DN, Mullen B, Yu H, Srigley J, Jarvi K: Seminal plasma biochemical markers and their association with semen analysis findings. Urology 1999, 53:596-603.
• [49]Alves MG, Martins AD, Rato L, Moreira PI, Socorro S, Oliveira PF: Molecular mechanisms beyond glucose transport in diabetes-related male infertility. Biochim Biophys Acta 1832, 2013:626-635.