Mechanisms of obesity-induced male infertility

References

• Adamson GD, Baker VL. Subfertility: causes, treatment and outcome. Best Pract. Res. Clin. Obstet Gynaecol.17, 169–185 (2003).
   PubMed Web of Science ®Google Scholar
• Kasturi SS, Tannir J, Brannigan RE. The metabolic syndrome and male infertility. J. Androl.29, 251–259 (2008).
   PubMedGoogle Scholar
• Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991–1998. JAMA282, 1519–1522 (1999).
   PubMed Web of Science ®Google Scholar
• Mokdad AH, Ford ES, Bowman BAet al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA289, 76–79 (2003).
   PubMed Web of Science ®Google Scholar
• Collins S. Overview of clinical perspectives and mechanisms of obesity. Birth Defects Res.73, 470–471 (2005).
   Google Scholar
• Naz RK, Rajesh PB. Role of tyrosine phosphorylation in sperm capacitation/acrosome reaction. Reprod. Biol. Endocrinol.9(2), 75 (2004).
   Google Scholar
• Visconte PE. Understanding the molecular basis of sperm capacitation through kinase design. PNAS106(3), 667–668 (2009).
   PubMedGoogle Scholar
• World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm – Cervical Mucus Interaction (4th Edition). Cambridge University Press, Cambridge, UK (1999).
   Google Scholar
• Carruthers M, Trinick TR, Jankowska E, Traish AM. Are the adverse effects of glitazones linked to induced testosterone deficiency? Cardiovasc. Diabetol.7, 30 (2008).
   PubMedGoogle Scholar
• Price TM, O’Brien SN, Welter BH, George R, Anandjiwala JK. Oestrogen regulation of adipose tissue lipoprotein lipase-possible mechanisms of body fat distribution. Am. J. Obstet. Gynecol.178, 101–107 (1998).
   PubMed Web of Science ®Google Scholar
• Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology144(11), 5081–5088 (2003).
   PubMed Web of Science ®Google Scholar
• Singh R, Artaza JN, Taylor WE et al. Testosterone inhibits adipogenic differentiation in 3T3- L1 cells: nuclear translocation of androgen receptor complex with β-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology147(1), 141–154 (2006).
   PubMed Web of Science ®Google Scholar
• McTernan PG, Anderson LA, Anwar AJ. Glucocorticoid regulation of P450 aromatase activity in human adipose tissue: gender and site differences. J. Clin. Endocrin. Metab.87(3), 1327–1336 (2002).
   PubMed Web of Science ®Google Scholar
• Oken E. Gillman MW. Fetal origins of obesity. Obes. Res.11, 496–506 (2003).
   PubMedGoogle Scholar
• Pauli EM, Legro RS, Demers LM, Kunselman AR, Dodson WC, Lee PA. Diminished paternity and gonadal function with increasing obesity in men. Fertil. Steril.90, 346–351 (2008).
   PubMed Web of Science ®Google Scholar
• Romero-Corral A, Lopez-Jimenez F, Sierra-Johnson J, Somers VK. Differentiating between body fat and lean mass-how should we measure obesity? Nat. Clin. Pract. Endocrinol. Metab.4, 322–323 (2008).
   PubMedGoogle Scholar
• Jensen TK, Andersson AM, Jorgensen Net al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil. Steril.82, 863–870 (2004).
   PubMed Web of Science ®Google Scholar
• Hammoud AO, Wilde N, Gibson M, Parks A, Carrell DT, Meikle AW. Male obesity and alteration in sperm parameters. Fertil. Steril.90(6), 2222–2225 (2008).
   PubMed Web of Science ®Google Scholar
• Kort HI, Massey JB, Elsner CW et al.Impact of body mass index values on sperm quantity and quality. J. Androl.27, 450–452 (2006).
   PubMedGoogle Scholar
• Koloszár S, Fejes I, Závaczki Z, Daru J, Szöllosi J, Pál A. Effect of body weight on sperm concentration in normozoospermic males. Arch. Androl.51, 299–304 (2005).
   PubMed Web of Science ®Google Scholar
• Hofny ER, Ali ME, Abdel-Hafez HZet al. Semen parameters and hormonal profile in obese fertile and infertile males. Fertil. Steril. DOI: 10.1016/j.fertstert.2009.03.085 (2009) (Epub ahead of print).
   PubMedGoogle Scholar
• 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.90, 619–626 (2008).
   PubMed Web of Science ®Google Scholar
• Duits FH, van Wely M, van der Veen F, Gianotten J. Healthy overweight male partners of subfertile couples should not worry about their semen quality. Fertil. Steril. DOI: 10.1016/j.fertnstert.2009.05.075 (2009) (Epub ahead of print).
   PubMedGoogle Scholar
• Nicopoulou SC, Alexiou M, Michalakis K et al. Body mass index vis-à-vis total sperm count in attendees of a single andrology clinic. Fertil. Steril.92(3), 1016–1017 (2009).
   PubMed Web of Science ®Google Scholar
• Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sørensen TI, Olsen J. Subfecundity in overweight and obese couples. Hum. Reprod.22(6), 1634–1637 (2007).
   PubMed Web of Science ®Google Scholar
• Sallmén M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiol.17(5), 520–523 (2006).
   PubMed Web of Science ®Google Scholar
• Nguyen RH, Wilcox AJ, Skjaerven R, Baird DD. Men’s body mass index and infertility. Human Reprod.22(9), 2488–2493 (2007).
   PubMed Web of Science ®Google Scholar
• Fejes I, Koloszar S, Zavackcski Z, Daru J, Szollosi J, Pal A. Effect of body weight on testosterone/estradiol ratio in olgozoospermic patients. Arch. Androl.52, 97–102 (2006).
   PubMed Web of Science ®Google Scholar
• 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.30, 439–444 (2007).
   PubMedGoogle Scholar
• Kley HK, Solbach HG, McKinnan JC, Krüskemper HL. Testosterone decrease and estrogen increase in male patients with obesity. Acta Endocrinol.91, 553–563, (1979).
   PubMedGoogle Scholar
• Zumoff B, Strain GW, Miller LK et al. Plasma free and non-SHBG-bound testosterone are decreased in obese men in proportion to their degree of obesity. J. Clin. Endocrinol. Metab.71, 929–931 (1990).
   PubMed Web of Science ®Google Scholar
• Strain GW, Zumoff B, Miller LK et al. Effect of massive weight loss on hypothalamic–pituitary–gonadal function in obese men. J. Clin. Endocrinol. Metab.66, 1019–1023 (1988).
   PubMed Web of Science ®Google Scholar
• Zumoff B, Strain GW. A perspective on the hormonal abnormalities of obesity: are they cause or effect? Obes. Res.2, 56–67, (1994).
   PubMedGoogle Scholar
• Schneider G, Kirschner MA, Berkowitz R, Ertel NH. Increased estrogen production in obese men. J. Clin. Endocrinol. Metab.48, 633–638 (1979).
   PubMed Web of Science ®Google Scholar
• Zumoff B, Strain GW, Kream J, O’Connor J, Levin J, Fukushima DK. Obese young men have elevated plasma estrogen levels, but obese premenopausal women do not. Metabolism30, 1011– 1014 (1981).
   PubMedGoogle Scholar
• Strain GW, Zumoff B, Kream Jet al. Mild hypogonadotropic hypogonadism in obese men. Metabolism31, 871–875 (1982).
   PubMed Web of Science ®Google Scholar
• Jung A, Schuppe HC. Influence of genital heat stress on semen quality in humans. Andrologia39(6), 203–215 (2007).
   PubMed Web of Science ®Google Scholar
• Gat Y, Zukerman Z, Chakraborty J, Gornish M. Varicocele, hypoxia and male infertility. Fluid mechanics analysis of the impaired testicular venous drainage system. Hum. Reprod.20(9), 2614–2619 (2005).
   PubMed Web of Science ®Google Scholar
• Petak SM, Nankin HR, Spark RF et al.American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr. Pract.8, 439–456 (2002).
   Google Scholar
• Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. Tissue distribution and quantitative analysis of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) messenger ribonucleic acid in the wild-type and ERα-knockout mouse. Endocrinology138, 4613–4621 (1997).
   PubMed Web of Science ®Google Scholar
• Laflamme N, Nappi RE, Drolet G, Labrie C, Rivest S. Expression and neuropeptidergic characterization of estrogen receptors (ERα and ERβ) throughout the rat brain: anatomical evidence of distinct roles of each subtype. J. Neurobiol.36, 357–378 (1998).
   PubMedGoogle Scholar
• Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J. Comp. Neurol.388, 507–525 (1997).
   PubMed Web of Science ®Google Scholar
• Strain GW, Zumoff B. The effect of bariatric surgery on the abnormalities of the pituitary–gonadal axis in obese men. Surg. Obes. Relat. Dis.2(2), 75–77 (2006).
   PubMedGoogle Scholar
• Cohen PG. The hypogonadal–obesity cycle: role of aromatase in modulating the testosterone–estradiol shunt – a major factor in the genesis of morbid obesity. Med. Hypotheses52(1), 49–51 (1999).
   PubMed Web of Science ®Google Scholar
• Marin P, Oden B, Bjorntorp P. Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J. Clin. Endocrinol. Metab.80, 239–243 (1995).
   PubMed Web of Science ®Google Scholar
• Kapoor D, Channer KS, Jones TH. Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with Type 2 diabetes. Diabetes Vasc. Dis. Res.5(2), 135–137 (2008).
   PubMed Web of Science ®Google Scholar
• Cohen PG. Aromatase, adiposity, aging and disease. The hypogonadal–metabolic–atherogenic-disease and aging connection. Med. Hypotheses56(6), 702–708 (2001).
   PubMed Web of Science ®Google Scholar
• Hammoud AO, Gibson, M, Hunt SC, Carrell D, Adamas TD, Meikle W. Effect of weight loss after Roux-en-Y gastric bypass surgery on the male reproductive hormonal profile. Fertil. Steril.88, S1–S2 (2007)
   PubMedGoogle Scholar
• Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat. Clin. Pract. Endocrinol. Metab.4, 415–419 (2008).
   PubMedGoogle Scholar
• de Boer H, Verschoor L, Ruinemans-Koerts J, Jansen M. Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes Obes. Metab.7, 211–215 (2005).
   PubMed Web of Science ®Google Scholar
• Bierman EL, Bagdade JD, Porte D Jr. Obesity and diabetes: the odd couple. Am. J. Clin. Nutr.21(12), 1434–1437 (1968).
   PubMed Web of Science ®Google Scholar
• Pasquali R, Casimirri F, De Iasio R et al. Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. J. Clin. Endocrinol. Metab.80(2), 654–658 (1995)
   PubMed Web of Science ®Google Scholar
• Haffner SM, Shaten J, Stern MP, Smith GD, Kuller L. Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial. Am. J. Epidemiol.143, 889–897 (1996).
   PubMed Web of Science ®Google Scholar
• Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. 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 Care23, 490–494 (2000).
   PubMed Web of Science ®Google Scholar
• Oh JY, Barrett-Connor E, Wedick NM, Wingard DL; Rancho Bernardo Study. Endogenous sex hormones and the development of Type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care25, 55–60 (2002).
   PubMed Web of Science ®Google Scholar
• Laaksonen DE, Niskanen L, Punnonen K et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care27(5), 1036–1041 (2004).
   PubMed Web of Science ®Google Scholar
• 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.6(3), 208–215 (2004).
   PubMed Web of Science ®Google Scholar
• Laaksonen DE, Niskanen L, Punnonen K et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur. J. Endocrinol.149(6), 601–608 (2003).
   PubMed Web of Science ®Google Scholar
• Barrett-Connor E, Khaw KT, Yen SS. Endogenous sex hormone levels in older men with diabetes mellitus. Am. J. Epidem.132, 895–901 (1990).
   PubMed Web of Science ®Google Scholar
• Andersson B, Marin P, Lissner L, Vermeulen A, Bjorntorp P. Testosterone concentrations in women and men with NIDDM. Diabetes Care17, 405–411 (1994).
   PubMed Web of Science ®Google Scholar
• Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in Type 2 diabetes. J. Clin. Endocrin. Met.89, 5462–5468 (2004).
   PubMed Web of Science ®Google Scholar
• 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 Care27, 861–868 (2004).
   PubMed Web of Science ®Google Scholar
• Osuna JA, Gomez-Perez R, Arata-Bellabarba G, Villaroel V. Relationship between BMI, total testosterone, sex hormone binding-globulin, leptin, insulin and insulin resistance in obese men. Arch. Androl.52, 355–361 (2006).
   PubMedGoogle Scholar
• Yeap BB, Chubb SA, Hyde Zet al. Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study. Eur. J. Endocrinol.161, 591–598 (2009).
   PubMed Web of Science ®Google Scholar
• Pitteloud N, Mootha VK, Dwyer AA et al.Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care28, 1636–1642 (2005).
   PubMed Web of Science ®Google Scholar
• Pitteloud N, Hardin M, Dwyer AA et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J. Clin. Endocrinol. Metab.90, 2636–2641 (2005).
   PubMed Web of Science ®Google Scholar
• Lin T, Vinson N, Terracio L. Characterization of insulin and insulin-like growth factor receptors in purified Leydig cells and their role in steroidogenesis in primary culture: a comparative study. Endocrinology119, 1641–1647 (1986).
   PubMed Web of Science ®Google Scholar
• Bebakar WM, Honour JW, Foster D, Liu YL, Jacobs HS. Regulation of testicular function by insulin and transforming growth factor-β. Steroids55, 266–269 (1990).
   PubMed Web of Science ®Google Scholar
• Burcelin R, Thorens B, Glauser M, Gaillard RC, Pralong FP. Gonadotropin-releasing hormone secretion from hypothalamic neurons stimulation by insulin and potentiation by leptin. Endocrinology144, 4484–4491 (2003).
   PubMed Web of Science ®Google Scholar
• Echavarría Sánchez MG, Franco Laguna E, Juárez Bengoa A, Villanueva Díaz CA. Seminal quality and hormones in patients with diabetes mellitus Type 2. Ginecol. Obstet. Mex.75, 241–246 (2007).
   PubMedGoogle Scholar
• Ali ST, Shaikh RN, Siddiqi NA, Siddiqi PQ. Semen analysis in insulin-dependent/non-insulin-dependent diabetic men with/without neuropathy. Arch. Androl.30, 47–54 (1993).
   PubMed Web of Science ®Google Scholar
• Vignon F, Le Faou A, Montagnon D et al. Comparative study of semen in diabetic and healthy men. Diabetes Metab.17, 350–354 (1991).
   Google Scholar
• Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature372, 425–432 (1994).
   PubMed Web of Science ®Google Scholar
• Lee GH, Proenca R, Montez JM et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature379, 632–635 (1996).
   PubMed Web of Science ®Google Scholar
• Wang MY, Zhou YT, Newgard CB, Unger, RH. A novel leptin receptor isoform in rat. FEBS Lett.392, 87–90 (1998).
   Google Scholar
• Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem. J.393(Pt 1), 7–20 (2006).
   PubMed Web of Science ®Google Scholar
• Tartaglia LA. The leptin receptor. J. Biol. Chem.272(10), 6093–6096 (1997).
   PubMed Web of Science ®Google Scholar
• Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J. Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem. Biophys. Res. Commun.283(4), 982–988 (2001).
   PubMed Web of Science ®Google Scholar
• Halaas JL, Gajiwala KS, Maffei M et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science269(5223), 543–546 (1995).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M, Barreiro ML. Leptin in male reproduction: the testis paradigm. Mol. Cell. Endocrinol.188(1–2), 9–13 (2002).
   PubMed Web of Science ®Google Scholar
• Cohen P, Zhao C, Cai Xet al. Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest.108, 1113–1121 (2001).
   PubMed Web of Science ®Google Scholar
• Chua SC, Chung WK, Wu-Peng XSet al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science271, 994–996 (1996).
   PubMed Web of Science ®Google Scholar
• Gibson WT, Farooqi IS, Moreau Met al. Congenital leptin deficiency due to homozygosity for the δ133G mutation: report of another case and evaluation of response to four years of leptin therapy. J. Clin. Endocrinol. Metab.89(10), 4821–4826 (2004).
   PubMed Web of Science ®Google Scholar
• Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat. Genet.18, 213–215 (1998).
   PubMed Web of Science ®Google Scholar
• Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab.84(10), 3686–3695 (1999).
   PubMed Web of Science ®Google Scholar
• Mazen I, El-Gammal M, Abdel-Hamid M, Amr K. A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient. Mol. Genet. Metab.97(4), 305–308 (2009).
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Wangensteen T, Collins Set al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N. Engl. J. Med.356(3), 237–247 (2007).
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Jebb SA, Langmack Get al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med.341, 879–884 (1999).
   PubMed Web of Science ®Google Scholar
• Farooqi IS, Matarese G, Lord GMet al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest.110, 1093–1103 (2002).
   PubMed Web of Science ®Google Scholar
• Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int. J. Obes. Relat. Metab. Disord.26, 1407–1433 (2002).
   PubMed Web of Science ®Google Scholar
• Isidori A, Fabbri A. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J. Clin. Endocrinol. Metab.84, 3673–3680 (1999).
   PubMed Web of Science ®Google Scholar
• Vettor R, De Pergola G, Pagano Cet al. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur. J. Clin. Invest.27, 1016–1024 (1997).
   PubMed Web of Science ®Google Scholar
• 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.30(5), 439–444 (2007).
   PubMedGoogle Scholar
• Hanafy S, Halawa FA, Mostafa T, Mikhael NW, Khalil KT. Serum leptin correlates in infertile oligozoospermic males. Andrologia39(5), 177–180 (2007).
   PubMed Web of Science ®Google Scholar
• Caro JF, Kolaczynski JW, Nyce MRet al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet348(9021), 159–161 (1996).
   PubMed Web of Science ®Google Scholar
• Jéquier E. Leptin signaling, adiposity, and energy balance. Ann. NY Acad. Sci.967, 379–388 (2002).
   PubMed Web of Science ®Google Scholar
• Couce ME, Green D, Brunetto A, Achim C, Lloyd RV, Burguera B. Limited brain access for leptin in obesity. Pituitary4(1–2), 101–110 (2001).
   PubMedGoogle Scholar
• Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides17(2), 305–311 (1996).
   PubMed Web of Science ®Google Scholar
• Banks WA. The blood–brain barrier as a cause of obesity. Curr. Pharm. Des.14(16), 1606–1614 (2008).
   PubMedGoogle Scholar
• Wong ML, Licinio J, Yildiz BOet al. Simultaneous and continuous 24-hour plasma and cerebrospinal fluid leptin measurements: dissociation of concentrations in central and peripheral compartments. J. Clin. Endocrinol. Metab.89(1), 258–265 (2004).
   PubMed Web of Science ®Google Scholar
• Kalra SP. Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions. Peptides29(1), 127–138 (2008).
   PubMed Web of Science ®Google Scholar
• Cunningham MJ, Clifton DK, Steiner RA. Leptin’s actions on the reproductive axis: perspectives and mechanisms. Biol. Reprod.60(2), 216–222 (1999).
   PubMed Web of Science ®Google Scholar
• Sweeney G. Leptin signalling. Cell. Signall.14, 655–663 (2002).
   PubMed Web of Science ®Google Scholar
• Mounzih K, Lu R, Chehab FF. Leptin treatment rescues the sterility of genetically obese ob/ob males. Endocrinology138(3), 1190–1193 (1997).
   PubMed Web of Science ®Google Scholar
• Cleary MP, Bergstrom HM, Dodge TL, Getzin SC, Jacobson MK, Phillips FC. Restoration of fertility in young obese (Lep(ob) Lep(ob)) male mice with low dose recombinant mouse leptin treatment. Int. J. Obes. Relat. Metab. Disord.25(1), 95–97 (2001).
   PubMedGoogle Scholar
• Gottsch ML, Cunningham MJ, Smith JTet al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology145(9), 4073–4077 (2004).
   PubMed Web of Science ®Google Scholar
• Kotani M, Detheux M, Vandenbogaerde Aet al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J. Biol. Chem.276(37), 34631–34636 (2001).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M. GPR54 and kisspeptin in reproduction. Hum. Reprod. Update12(5), 631–639 (2006).
   PubMed Web of Science ®Google Scholar
• Smith JT, Acohido BV, Clifton DK, Steiner RA. KiSS-1 neurones are direct targets for leptin in the ob/ob mouse. J. Neuroendocrinol.18(4), 298–303 (2006).
   PubMed Web of Science ®Google Scholar
• Quennell JH, Mulligan AC, Tups Aet al. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology150(6), 2805–2812 (2009).
   PubMed Web of Science ®Google Scholar
• Tapanainen JS, Tilly JL, Vihko KK, Hsueh AJW. Hormonal control of apoptotic cell death in the testis: gonadotropins and androgens as testicular cell survival factors. Mol. Endocrinol.7, 643–650 (1993).
   PubMed Web of Science ®Google Scholar
• Sinha Hikim AP, Swerdloff RS. Hormonal and genetic control of germ cell apoptosis in the testis. Rev. Reprod.4(1), 38–47 (1999).
   PubMedGoogle Scholar
• Yan W, Samson M, Jégou B, Toppari J. Bcl-w forms complexes with Bax and Bak, and elevated ratios of Bax/Bcl-w and Bak/Bcl-w correspond to spermatogonial and spermatocyte apoptosis in the testis. Mol. Endocrinol.14(5), 682–699 (2000).
   PubMedGoogle Scholar
• Sofikitis N, Giotitsas N, Tsounapi P, Baltogiannis D, Giannakis D, Pardalidis N. Hormonal regulation of spermatogenesis and spermiogenesis. J. Steroid Biochem. Mol. Biol.109(3–5), 323–330 (2008).
   PubMed Web of Science ®Google Scholar
• Bhat GK, Sea TL, Olatinwo MOet al. Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse. J. Androl.27(2), 302–310 (2006).
   PubMedGoogle Scholar
• Lee J, Richburg JH, Younkin SC, Boekelheide K. The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology138, 2081–2088 (1997).
   PubMed Web of Science ®Google Scholar
• Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia39, 22–27 (2007).
   PubMed Web of Science ®Google Scholar
• Herrid M, O’Shea T, McFarlane JR. Ontogeny of leptin and its receptor expression in mouse testis during the postnatal period. Mol. Reprod. Dev.75(5), 874–880 (2008).
   PubMed Web of Science ®Google Scholar
• Banks WA, McLay RN, Kastin AJ, Sarmiento U, Scully S. Passage of leptin across the blood–testis barrier. Am. J. Physiol.276, E1099–E1104 (1999).
   PubMed Web of Science ®Google Scholar
• El-Hefnawy T, Ioffe S, Dym M. Expression of the leptin receptor during germ cell development in the mouse testis. Endocrinology141, 2624–2630 (2000).
   PubMed Web of Science ®Google Scholar
• Caprio M, Fabbrini E, Ricci Get al. Ontogenesis of leptin receptor in rat Leydig cells. Biol. Reprod.68(4), 1199–1207 (2003).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M, Pinilla L, Zhang FPet al. Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis. Biol. Reprod.64, 634–643 (2001).
   PubMed Web of Science ®Google Scholar
• Glander HJ, Lammert A, Paasch U, Glasow A, Kratzsch J. Leptin exists in tubuli seminiferi and in seminal plasma. Andrologia34, 227–233 (2002).
   PubMed Web of Science ®Google Scholar
• Cioffi JA, Shafer AW, Zupancic TJet al. Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat. Med.2, 585–589 (1996).
   PubMed Web of Science ®Google Scholar
• O’Donnell L, Robertson KM, Jones ME, Simpson ER. Estrogen and spermatogenesis. Endocr. Rev.22, 289–318 (2001).
   PubMed Web of Science ®Google Scholar
• Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of functional leptin receptors in rodent Leydig cells. Endocrinology140, 4939–4947 (1999).
   PubMed Web of Science ®Google Scholar
• Herrid M, Xia Y, O’Shea T, McFarlane JR. Leptin inhibits basal but not gonadotrophin-stimulated testosterone production in the immature mouse and sheep testis. Reprod. Fertil. Dev.20(4), 519–528 (2008).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M, Pinilla L, Gonzalez LC, Dieguez C, Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. J. Endocrinol.161, 211–218 (1999).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M, Pinilla L, González LCet al.In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin (116–130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat. Eur. J. Endocrinol.142(4), 406–410 (2000).
   PubMedGoogle Scholar
• Ahima RS, Osei SY. Leptin signaling. Physiol. Behav.81, 223–241(2004).
   PubMed Web of Science ®Google Scholar
• Bjørbæck C, Uotani S, da Silva B, Flier JS. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem.272, 32686–32695 (1997).
   PubMedGoogle Scholar
• Bjørbæck C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Rec. Prog. Horm. Res.59, 305–331 (2004).
   PubMedGoogle Scholar
• Ghilardi N, Skoda RC. The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol. Endocrinol.11, 393–399 (1997).
   PubMed Web of Science ®Google Scholar
• Aquila S, Rago V, Guido C, Casaburi I, Zupo S, Carpino A. Leptin and leptin receptor in pig spermatozoa: evidence of their involvement in sperm capacitation and survival. Reproduction136(1), 23–32 (2008).
   PubMed Web of Science ®Google Scholar
• Ruiz-Cortés ZT, Martel-Kennes Y, Gévry NY, Downey BR, Palin MF, Murphy BD. Biphasic effects of leptin in porcine granulosa cells. Biol. Reprod.68(3), 789–796 (2003).
   PubMed Web of Science ®Google Scholar
• Stocco DM, Wang X, Jo Y, Manna PR. Multiple signaling pathways regulating steroidogenesis and steroidogenic acute regulatory protein expression: more complicated than we thought. Mol. Endocrinol.19(11), 2647–2659 (2005).
   PubMed Web of Science ®Google Scholar
• Matsuda T, Nakamura T, Nakao Ket al. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J.18(15), 4261–4269 (1999).
   PubMed Web of Science ®Google Scholar
• Tena-Sempere M, Pinilla L, Zhang FPet al. Developmental and hormonal regulation of leptin receptor (Ob-R) messenger ribonucleic acid expression in rat testis. Biol. Reprod.64(2), 634–643 (2001).
   PubMed Web of Science ®Google Scholar
• von Sobbe HU, Koebnick C, Jenne L, Kiesewetter F. Leptin concentrations in semen are correlated with serum leptin and elevated in hypergonadotrophic hypogonadism. Andrologia35(4), 233–237 (2003).
   PubMedGoogle Scholar
• Ando 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.245, 1–6 (2005).
   PubMed Web of Science ®Google Scholar
• Aquila S, Gentile M, Middea Eet al. Leptin secretion by human spermatozoa. J. Clin. Endocrinol. Metab.90, 4753–4761 (2005).
   PubMed Web of Science ®Google Scholar
• Chen B, Guo JH, Lu YNet al. Leptin and varicocele-related spermatogenesis dysfunction: animal experiment and clinical study. Int. J. Androl32(5), 532–541 (2008).
   PubMedGoogle Scholar
• Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development121, 1129–1137 (1995).
   PubMed Web of Science ®Google Scholar
• De Ambrogi M, Spinaci M, Galeati G, Tamanini C. Leptin receptor in boar spermatozoa. Int. J. Androl.30, 458–461 (2007).
   PubMedGoogle Scholar
• Li HW, Chiu PC, Cheung MP, Yeung WS, O WS. Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa. Int. J. Androl.32(6), 687–694 (2008).
   PubMedGoogle Scholar
• Jope T, Lammert A, Kratzsch J, Paasch U, Glander HJ. Leptin and leptin receptor in human seminal plasma and in human spermatozoa. Int. J. Androl.26, 335–341 (2003).
   PubMedGoogle Scholar
• Hjollund NH, Storgaard L, Ernst E, Bonde JP, Olsen J. Impact of diurnal scrotal temperature on semen quality. Reprod. Toxicol.16(3), 215–221 (2002).
   PubMedGoogle Scholar
• Jung A, Schill WB, Schuppe HC. Genital heat stress in men of barren couples: a prospective evaluation by means of a questionnaire. Andrologia34(6), 349–355 (2002).
   PubMedGoogle Scholar
• Carlsen E, Andersson AM, Petersen JH, Skakkebaek NE. History of febrile illness and variation in semen quality. Hum. Reprod.18(10), 2089–2092 (2003).
   PubMed Web of Science ®Google Scholar
• Hjollund NH, Bonde JP, Jensen TK, Olsen J. Diurnal scrotal skin temperature and semen quality. The Danish First Pregnancy Planner Study Team. Int. J. Androl.23(5), 309–318 (2000).
   PubMedGoogle Scholar
• Hjollund NH, Storgaard L, Ernst E, Bonde JP, Olsen J. The relation between daily activities and scrotal temperature. Reprod. Toxicol.16(3), 209–214 (2002).
   PubMed Web of Science ®Google Scholar
• Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Heimisdottir M, Olafsdottir K. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum. Reprod.20(1), 208–215 (2005).
   PubMed Web of Science ®Google Scholar
• Lue YH, Hikim AP, Swerdloff RSet al. Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology140, 1709–1717 (1999).
   PubMed Web of Science ®Google Scholar
• Paul C, Melton DW, Saunders PT. Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility? Mol. Hum. Reprod.14(1), 1–8 (2008).
   PubMed Web of Science ®Google Scholar
• Paul C, Teng S, Saunders PT. A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol. Reprod80(5), 913–919 (2009).
   PubMed Web of Science ®Google Scholar
• Yin Y, Hawkins KL, DeWolf WC, Morgentaler A. Heat stress causes testicular germ cell apoptosis in adult mice. J. Androl.18(2), 159–165 (1997).
   PubMed Web of Science ®Google Scholar
• Zhu BK, Setchell BP. Effects of paternal heat stress on the in vivo development of preimplantation embryos in the mouse. Reprod. Nut. Dev.44, 617–629 (2004).
   PubMedGoogle Scholar
• Cammack KM, Mesa H, Lamberson WR. Genetic variation in fertility of heat-stressed male mice. Theriogenology66, 2195–2201 (2006).
   PubMed Web of Science ®Google Scholar
• Eddy EM. Role of heat shock protein HSP70-2 in spermatogenesis. Rev. Reprod.4(1), 23–30 (1999).
   PubMedGoogle Scholar
• Georgopoulos C, Welch WJ. Role of the major heat shock proteins as molecular chaperones. Annu. Rev. Cell. Biol.9, 601–634 (1993).
   PubMedGoogle Scholar
• Vydra N, Malusecka E, Jarzab Met al. Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells. Cell Death Differ.13(2), 212–222 (2006).
   PubMed Web of Science ®Google Scholar
• Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol. Cell. Biol.17(9), 5317–5327 (1997).
   PubMed Web of Science ®Google Scholar
• Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol. Reprod.65, 229–239 (2001).
   PubMed Web of Science ®Google Scholar
• Izu H, Inouye S, Fujimoto M, Shiraishi K, Naito K, Nakai A. Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells. Biol. Reprod.70, 18–24 (2004).
   PubMed Web of Science ®Google Scholar
• Fernandes M, Xiao H, Lis JT. Fine structure analyses of the Drosophila and Saccharomyces heat shock factor – heat shock element interactions. Nucleic Acids Res.22(2), 167–173 (1994).
   PubMed Web of Science ®Google Scholar
• Salmand PA, Jungas T, Fernandez M, Conter A, Christians ES. 2008 Mouse heat-shock factor 1 (HSF1) is involved in testicular response to genotoxic stress induced by doxorubicin. Biol. Reprod.79(6), 1092–1101.
   PubMedGoogle Scholar
• Widlak W, Winiarski B, Krawczyk A, Vydra N, Malusecka E, Krawczyk Z. Inducible 70 kDa heat shock protein does not protect spermatogenic cells from damage induced by cryptorchidism. Int. J. Androl.30(2), 80–87 (2007).
   PubMedGoogle Scholar
• Tramontano F, Malanga M, Farina B, Jones R, Quesada P. Heat stress reduces poly (ADPR)polymerase expression in rat testis. Mol. Hum. Reprod.6(7), 575–581 (2000).
   PubMed Web of Science ®Google Scholar
• Jia Y, Castellanos J, Wang Cet al. Mitogen-activated protein kinase signaling in male germ cell apoptosis in the rat. Biol. Reprod.80(4), 771–780 (2009).
   PubMedGoogle Scholar
• Johnson C, Jia Y, Wang Cet al. Role of caspase 2 in apoptotic signaling in primate and murine germ cells. Biol. Reprod.79(5), 806–814 (2008).
   PubMed Web of Science ®Google Scholar
• Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A. The enigma of caspase-2: the laymen’s view. Cell. Death Differ.16(2), 195–207 (2009).
   PubMed Web of Science ®Google Scholar
• Weidemann A, Johnson RS. Biology of HIF-1α. Cell. Death Differ.15, 621–627 (2008).
   PubMed Web of Science ®Google Scholar
• Setchell BP. The Parkes Lecture. Heat and the testis. J. Reprod. Fert.114, 179–194 (1998).
   PubMedGoogle Scholar
• Paul C, Murray AA, Spears N, Saunders PT. A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction136(1), 73–84 (2008).
   PubMed Web of Science ®Google Scholar
• Carlsen E, Giwereman A, Keiding N, Skakkebaek NE. Evidence for decreasing sperm quality of semen during the past 50 years. Br. Med. J.304, 609–613 (1992).
   PubMed Web of Science ®Google Scholar
• US Environmental Protection Agency. Special Report on Environmental Endocrine Disruption: an Effects Assessment and Analysis. Office of Research and Development. Washington, DC, USA, EPA/630/R-96/012 (1997).
   Google Scholar
• WHO. Global assessment of the state-of-the-sience of endocrine disruptors. International Programme on Chemical Safety. Damstra T, Barlow S, Bergman A, Kavlock R, Van Der Kraak G (Eds). WHO, Geneva, Switzerland (2002).
   Google Scholar
• Phillips KP, Tanphaichitr N. Human exposure to endocrine disrupters and semen quality. J. Toxicol. Environ. Health B Crit. Rev.11(3–4), 188–220 (2008).
   PubMed Web of Science ®Google Scholar
• Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J. Altern. Comp. Med.8, 185–192 (2002).
   PubMed Web of Science ®Google Scholar
• Newbold R, Padilla-Banks E, Snyder RJ, Phillips TM, Jefferson WN. Developmental exposure to endocrine disruptors and the obesity epidemic. Reprod. Toxicol.23, 290–296 (2007).
   PubMed Web of Science ®Google Scholar
• Newbold R, Padilla-Banks E, Snyder RJ, Jefferson WN. Perinatal exposure to environmental estrogens and the development of obesity. Mol. Nut. Food Res.51, 912–917 (2007).
   PubMed Web of Science ®Google Scholar
• Barker DJ, Eriksson JG, Forsen T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int. J.Epidemiol.31, 1235–1239 (2002).
   PubMed Web of Science ®Google Scholar
• Gluckman PD, Hanson MA. Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Ped. Res.56, 311–317 (2004).
   PubMed Web of Science ®Google Scholar
• Hanson M, Gluckman P, Bier Det al. Report on the 2nd World Congress on Fetal Origins of Adult Disease, Brighton, UK, June 7–10, 2003. Ped. Res.55, 894–897 (2004).
   PubMedGoogle Scholar
• Pryor JL, Hughes C, Foster W, Hales BF, Robaire B. Critical windows of exposure for children’s health: the reproductive system in animals and humans. Environ. Health Perspect.108, 491–503 (2000).
   PubMed Web of Science ®Google Scholar
• Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: An increasingly common developmental disorder with environmental aspects. Hum. Reprod.16, 972–978 (2001).
   PubMed Web of Science ®Google Scholar
• Newbold RR, Padilla-Banks E, Jefferson WN, Heindel JJ. Effects of endocrine disruptors on obesity. Int. J. Androl.31(2), 201–208 (2008).
   PubMed Web of Science ®Google Scholar
• Goyal HO, Braden TD, Williams CS et al. Abnormal morphology of the penis in male rats exposed neonatally to diethylstilbestrol is associated with altered profile of estrogen receptor-α protein, but not of androgen receptor protein: a developmental and immunocytochemical study. Biol. Reprod.70, 1504–1517 (2004).
   PubMed Web of Science ®Google Scholar
• Goyal HO, Braden TD, Williams CS, Dalvi P, Mansour MM, Williams JW. Permanent induction of morphological abnormalities in the penis and penile skeletal muscles in adult rats treated neonatally with diethylstilbestrol or estradiol valerate: a dose–response study. J. Androl.26, 32–43 (2005).
   PubMedGoogle Scholar
• Goyal HO, Braden TD, Williams CS, Dalvi P, Mansour M, Williams JW. Estrogen-induced abnormal accumulation of fat cells in the rat penis and associated loss of fertility depends upon estrogen exposure during critical period of penile development. Toxicol. Sci.87(1), 242–254 (2005).
   PubMed Web of Science ®Google Scholar
• Goyal HO, Braden TD, Cooke PS et al. Estrogen receptor α mediates estrogen-inducible abnormalities in the developing penis. Reprod.133(5), 1057–1067 (2007).
   PubMedGoogle Scholar
• Mansour MM, Goyal HO, Braden TD et al.Activation of penile proadipogenic peroxisome proliferator-activated receptor γ with an estrogen: interaction with estrogen receptor α during postnatal development. PPAR Res.2008, 651419 (2008).
   PubMedGoogle Scholar
• Li D, Kang Q, Wang DM. Constitutive coactivator of peroxisome proliferator-activated receptor (PPARγ), a novel coactivator of PPARγ that promotes adipogenesis. Mol. Endocrinol.21(10), 2320–2333 (2007).
   PubMedGoogle Scholar
• Keller H, Givel F, Perroud M, Wahli W. Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements. Mol. Endocrinol.9(7), 794–804 (1995).
   PubMed Web of Science ®Google Scholar
• Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl Acad. Sci. USA93(12), 5925–5930 (1996).
   PubMed Web of Science ®Google Scholar
• Kuiper GG, Carlsson B, Grandien K et al.Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology138(3), 863–870 (1997).
   PubMed Web of Science ®Google Scholar
• Kraus WL, Weis KE, Katzenellenbogen BS. Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors. Mol. Cell. Biol.15(4), 1847–1857 (1995).
   PubMed Web of Science ®Google Scholar
• Feige JN, Gelman L, Rossi D et al. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor γ modulator that promotes adipogenesis. J. Biol. Chem.282(26), 19152–19166 (2007).
   PubMed Web of Science ®Google Scholar
• Grün F, Blumberg B. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev. Endocr. Metab. Disord.8(2), 161–171 (2007).
   PubMed Web of Science ®Google Scholar
• Grün F, Blumberg B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology147, S50–S55 (2006).
   PubMed Web of Science ®Google Scholar
• Müllerová D, Kopecký J. White adipose tissue: storage and effector site for environmental pollutants. Physiol. Res. 56(4), 375–381 (2007).
   Google Scholar
• Ryu JY, Whang J, Park H et al. Di (2-ethylhexyl) phthalate induces apoptosis through peroxisome proliferators-activated receptor-γ and ERK 1/2 activation in testis of Sprague-Dawley rats. J. Toxicol. Environ. Health A.70(15–16), 1296–1303 (2007).
   PubMed Web of Science ®Google Scholar
• Matthiessen P, Gibbs P. Critical appraisal of the evidence for tributyltinmediated endocrine disruption in mollusks. Environ. Toxicol. Chem.17, 37–43 (1998).
   Web of Science ®Google Scholar
• Grün F, Watanabe H, Zamanian Z et al. Endocrine disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol. Endocrinol.20, 2141–2155 (2006).
   PubMed Web of Science ®Google Scholar
• Tabb MM, Blumberg B. New modes of action for endocrine-disrupting chemicals. Mol. Endocrinol.20(3), 475–482 (2006).
   PubMed Web of Science ®Google Scholar
• Nakanishi T. Endocrine disruption induced by organotin compounds: organotin’s function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor. J. Toxicol. Sci.33(3), 269–276 (2008).
   PubMed Web of Science ®Google Scholar
• Remillard RB, Bunce NJ. Linking dioxins to diabetes: epidemiology and biologic plausibility. Environ. Health Perspect.110(9), 853–858 (2002).
   PubMed Web of Science ®Google Scholar
• Dang ZC, Audinot V, Papapoulos SE, Boutin JA, Lowik CW. Peroxisome proliferator-activated receptor γ (PPAR γ) as a molecular target for the soy phytoestrogen genistein. J. Biol. Chem.278, 962–967 (2003).
   PubMed Web of Science ®Google Scholar
• Phillips KP, Foster WG. Key developments in endocrine disrupter research and human health. J. Toxicol. Environ. Health B Crit. Rev.11(3–4), 322–344 (2008).
   PubMed Web of Science ®Google Scholar