The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility

Pachytene PIWI-interacting RNAs (piRNAs), which comprise >80% of small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like microRNAs, cleave targets like short interfering RNAs or lack biological function altogether. Although piRNA pathway protein mutants are male sterile, no biological function has been identified for any mammalian piRNA-producing locus. Here, we report that males lacking piRNAs from a conserved mouse pachytene piRNA locus on chromosome 6 (pi6) produce sperm with defects in capacitation and egg fertilization. Moreover, heterozygous embryos sired bypi6(-/-)fathers show reduced viability in utero. Molecular analyses suggest thatpi6piRNAs repress gene expression by cleaving messenger RNAs encoding proteins required for sperm function.pi6also participates in a network of piRNA-piRNA precursor interactions that initiate piRNA production from a second piRNA locus on chromosome 10, as well aspi6itself. Our data establish a direct role for pachytene piRNAs in spermiogenesis and embryo viability. Male mice lacking piRNAs from a conserved locus on chromosome 6 (pi6) produce sperm with defects in capacitation and egg fertilization.pi6piRNAs repress mRNAs required for sperm function.