Association of polymorphisms in the estrogen receptors alpha, and beta (ESR1, ESR2) with the occurrence of male infertility and semen parameters

作者：Safarinejad Mohammad Reza^*; Shafiei Nayyer; Safarinejad Shiva

来源：Journal of Steroid Biochemistry and Molecular Biology, 2010, 122(4): 193-203.

DOI：10.1016/j.jsbmb.2010.06.011

• Infertility
• Male factor
• Estrogen receptor
• ER-alpha
• ER-beta
• Polymorphism
• Genetic

Male infertility is a multifactorial condition with a strong genetic component. In the last decade a large number of investigations focused on the identification of gene variants affecting spermatogenesis in human. Polymorphisms of the estrogen receptor (ER) genes, have been implicated in male infertility, however, comprehensive data are lacking. We investigated the association between the ER-alpha gene (ESR1) Pvull and Xbal and ER-beta gene (ESR2) Rsal and Alul polymorphisms and the idiopathic male infertility in Iranian males. Polymerase chain reaction (PCR) method and restriction fragment length polymorphism (RFLP) were used to detect the ER-alpha, and ER-beta gene polymorphisms in 164 infertile men and 164 age-matched healthy controls. Reproductive hormones were measured and at least two semen analyses were performed in each subject. Significant differences were observed in the frequency distribution of Pvull and Xbal in the ESR-alpha gene and Rsal and Alul in the ER-beta gene between patients and controls. The presence of the ER-alpha Pvull TC (0R-0.56. 95% CI: 0.26-0.80; P=0.011), ER-alpha Xbal AG (OR=0.51, 95% CI: 0.31-0.84; P=0.017), and ER-beta Alul GC, (OR-0.48, 95% CI: 0.265-0.84; P=0.012) genotypes suggest a protective effect for infertility. The ER-beta Rsal AG (OR-2.32, 95% CI: 1.61-3.22; P=0.012) and ER-beta Alul AG (OR =2.76, 95% CI: 1.64-3.66; P=0.014) genotypes are associated with increased infertility risk Subjects (both fertile and infertile) with ER-alpha Pvull IT, ER-alpha Xbal AA. ER-beta Rsal AG, and ER-beta Alul AG genotypes had significantly lower levels of serum sex hormone binding globulin (SHBG), and luteinizing hormone (LH), but, higher serum levels of free estradiol and follicle stimulating hormone (FSH). The same genotypes had significantly lower values for sperm density, sperm motility, and percentage of sperm with normal morphology. Our results further suggest a possible role of ESR-alpha and ER-beta variants on male infertility. Further studies are needed to replicate our findings as well as to better elucidate the biological mechanisms of the modulation of ESR-alpha, and ER-beta on male infertility.

• 出版日期2010-10