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

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 () and Wenming Xu ()
Additional contact information
Ying Shen: Sichuan University
Feng Zhang: Fudan University
Fuping Li: Sichuan University
Xiaohui Jiang: Sichuan University
Yihong Yang: Sichuan University
Xiaoliang Li: Sichuan University
Weiyu Li: Fudan University
Xiang Wang: Sichuan University
Juan Cheng: Southwest Medical University
Mohan Liu: Sichuan University and Collaborative Innovation Center
Xueguang Zhang: Sichuan University
Guiping Yuan: Sichuan University
Xue Pei: Sichuan University and Collaborative Innovation Center
Kailai Cai: Chengdu Research Base of Giant Panda Breeding
Fengyun Hu: Auckland University
Jianfeng Sun: Teaching Hospital of Chengdu University of TCM
Lanzhen Yan: Chinese Academy of Sciences
Li Tang: Sichuan University
Chuan Jiang: Sichuan University
Wenling Tu: Sichuan University and Collaborative Innovation Center
Jinyan Xu: Sichuan University
Haojuan Wu: Southwest Medical University
Weiqi Kong: Sichuan University
Shuying Li: Sichuan University
Ke Wang: Sichuan University
Kai Sheng: Sichuan University
Xudong Zhao: Chinese Academy of Sciences
Huanxun Yue: Sichuan University
Xiaoyu Yang: The First Hospital, Nanjing Medical University
Wenming Xu: Sichuan University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-08182-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08182-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-08182-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().