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  • Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.

Nature communications (2019-01-27)
Ying Shen, Feng Zhang, Fuping Li, Xiaohui Jiang, Yihong Yang, Xiaoliang Li, Weiyu Li, Xiang Wang, Juan Cheng, Mohan Liu, Xueguang Zhang, Guiping Yuan, Xue Pei, Kailai Cai, Fengyun Hu, Jianfeng Sun, Lanzhen Yan, Li Tang, Chuan Jiang, Wenling Tu, Jinyan Xu, Haojuan Wu, Weiqi Kong, Shuying Li, Ke Wang, Kai Sheng, Xudong Zhao, Huanxun Yue, Xiaoyu Yang, Wenming Xu
PMID30683861
ABSTRACT

Aberrant sperm flagella impair sperm motility and cause male infertility, yet the genes which have been identified in multiple morphological abnormalities of the flagella (MMAF) can only explain the pathogenic mechanisms of MMAF in a small number of cases. Here, we identify and functionally characterize homozygous loss-of-function mutations of QRICH2 in two infertile males with MMAF from two consanguineous families. Remarkably, Qrich2 knock-out (KO) male mice constructed by CRISPR-Cas9 technology present MMAF phenotypes and sterility. To elucidate the mechanisms of Qrich2 functioning in sperm flagellar formation, we perform proteomic analysis on the testes of KO and wild-type mice. Furthermore, in vitro experiments indicate that QRICH2 is involved in sperm flagellar development through stabilizing and enhancing the expression of proteins related to flagellar development. Our findings strongly suggest that the genetic mutations of human QRICH2 can lead to male infertility with MMAF and that QRICH2 is essential for sperm flagellar formation.