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

J Steroid Biochem Mol Biol. 2010 Oct;122(4):193-203. doi: 10.1016/j.jsbmb.2010.06.011. Epub 2010 Jun 25.


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-α gene (ESR1) PvuII and XbaI and ER-β gene (ESR2) RsaI 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-α, and ER-β 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 XbaI in the ESR-α gene and RsaI and Alul in the ER-β gene between patients and controls. The presence of the ER-α Pvull TC (OR = 0.56, 95% CI: 0.26-0.80; P = 0.011), ER-α XbaI AG (OR = 0.51, 95% CI: 0.31-0.84; P = 0.017), and ER-β Alul GG (OR = 0.48, 95% CI: 0.265-0.84; P = 0.012) genotypes suggest a protective effect for infertility. The ER-β RsaI AG (OR = 2.32, 95% CI: 1.61-3.22; P = 0.012) and ER-β 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-α Pvull TT, ER-α XbaI AA, ER-β RsaI AG, and ER-β 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-α, and ER-β 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-α, and ER-β on male infertility.

MeSH terms

  • Adult
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / genetics*
  • Genotype
  • Haplotypes
  • Hormones / blood
  • Humans
  • Infertility, Male / genetics*
  • Iran
  • Male
  • Polymorphism, Genetic*
  • Semen / metabolism


  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Hormones