piRNA pathway disruption in human infertility

Abstract

PIWI-interacting RNAs (piRNAs) are crucial regulators of gene expression in male germ cells. In a study published in Nature Communications, the effect of disrupting piRNA biogenesis on human spermatogenesis was assessed. Analysis of exome data from >2,000 men with infertility led to the identification of biallelic variants in 14 genes related to the piRNA pathway in these men. These variants were associated with various testicular phenotypes, including non-obstructive azoospermia and cryptozoospermia. At a cellular level, dysfunction of piRNA-related genes resulted in reduced piRNA levels and de-repression of transposons in spermatogonia. The reproductive phenotypes of piRNA deregulation varied between mice and humans, highlighting that, although the piRNA pathway is conserved, species-specific research is still necessary. Results from this study show a prominent role of piRNA pathway genes in male infertility, providing potential targets for future investigations.