Home > Browse Issues > Vol.39 No.9
The Study of Human Piwi Mutations in Male Infertility
Gou Lantao, Kang Junyan, Liu Mofang*
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China
Abstract: Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals， but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline D-box mutations in human Piwi (Hiwi) in patients with azoospermia. By modeling such mutations in Piwi (Hiwi) knockin mice， we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically， we showthat D-box mutation caused-MIWI stabilization sequesters ring finger protein 8 (RNF8) in the cytoplasm of late spermatids， with blocking the ubiquitination and removal of histones. The failure of histone-to-protamine exchange finally leads to deficient spermiogenesis and male infertility. Collectively， our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.
CN
EN