Estrogen receptor β gene mutations in Indian infertile men

Recent studies suggest that estrogens play an important role in male fertility. Estrogen signaling is mediated by Estrogen Receptors (ER alpha and ER beta). Association of ER beta with male infertility has not been analyzed to date except for genotyping of known polymorphisms in two different studies, which yielded controversial interpretation. Hence, we performed sequencing of all the exons and untranslated regions of ER beta gene in 300 infertile and 255 fertile control Indian men. We identified eight novel mutations and four known single nucleotide polymorphisms (SNPs). Of the eight novel mutations, four were non-synonymous, of which one was detected only in infertile men, whereas the other three mutations were detected only in fertile men. Using different bioinformatics tools, we predicted that non-synonymous mutations were benign and they neither altered the structure nor the function of the protein. Among synonymous novel mutations, one was detected in both fertile and infertile men, two were exclusive to infertile men and one was exclusive to fertile men. None of the known SNPs or novel mutations showed statistically significant difference between infertile and fertile men. Moreover, infertile men having ER beta mutations had normal reproductive tract and serum hormone levels. Our results suggest that the SNPs and mutations in ER beta gene are not a common cause of spermatogenesis failure in Indian men, although mutations specifically found in infertile men can affect transcription, translation or have synergic effect with other variants in causing infertility.