Novel Mutations of TSPY1 Gene Associate Spermatogenic Failure Among Men

Abstract

Etiology of male infertility is intriguing owing to complex genetic regulation of human spermatogenesis and ethnic variations in genetic architecture of human populations. The present study characterizes the role of Y chromosome specific spermatogenic regulator testis-specific protein Y-encoded 1 (TSPY1) gene mutation in spermatogenic failure. This case-control study includes 163 cases of spermatogenic failure and 175 age-matched fertile men as controls. We found five novel base substitutions, namely, MT162695, MN879413, MN889982, MN889983, MN719943, two deletions MN734578 and MN734579, three novel insertions MN719941, MN719942 and MN719944 through Sanger's dideoxy sequencing of TSPY1 gene reading frame. All these mutations exhibited strong association with male infertility. In silico analyses suggest prospective disruption in splice sites and alteration in different isoforms of TSPY1 transcripts and amino acid sequence in TSPY1 protein. The study provides novel evidence in favour of implication of TSPY1 gene in male fertility. The outcome sheds light to get insight into the issue of idiopathic male infertility in Bengali population.

Keywords: Male infertility; Mutation; Polymorphisms; Spermatogenic failure; TSPY1 gene.