Alternative splicing and MicroRNA: epigenetic mystique in male reproduction

Infertility is rarely life threatening, however, it poses a serious global health issue posing far-reaching socio-economic impacts affecting 12-15% of couples worldwide where male factor accounts for 70%. Functional spermatogenesis which is the result of several concerted coordinated events to produce sperms is at the core of male fertility, Alternative splicing and microRNA (miRNA) mediated RNA silencing (RNAi) constitute two conserved post-transcriptional gene (re)programming machinery across species. The former by diversifying transcriptome signature and the latter by repressing target mRNA activity orchestrate a spectrum of testicular events, and their dysfunctions has several implications in male infertility. This review recapitulates the knowledge of these mechanistic events in regulation of spermatogenesis and testicular homoeostasis. In addition, miRNA payload in sperm, vulnerable to paternal inputs, including unhealthy diet, infection and trauma, creates epigenetic memory to initiate intergenerational phenotype. Naive zygote injection of sperm miRNAs from stressed father recapitulates phenotypes of offspring of stressed father. The epigenetic inheritance of paternal pathologies through miRNA could be a tantalizing avenue to better appreciate 'Paternal Origins of Health and Disease' and the power of tiny sperm.