Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA

Author:

Choi Heejin,Wang Zhengpin,Dean Jurrien

Abstract

AbstractpiRNAs are germline-specific, small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remains incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis and are sterile. The absence of Chr18 piRNA results in an imbalance of heat shock proteins associated with renaturing proteins and the ubiquitin-proteasome system involved with protein degradation. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of the trans-Golgi network, and up-regulation of GOLGA2 associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility.

Publisher

Cold Spring Harbor Laboratory

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