机构：[1]Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, 610041, Chengdu, China.[2]Obstetrics and Gynecology Hospital, Institute of Metabolism and Integrative Biology, School of Life Sciences, Fudan University, 200011, Shanghai, China.[3]State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 211116, Nanjing, China.[4]Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 200011, Shanghai, China.[5]Human Sperm Bank, West China Second University Hospital, Sichuan University, 610041, Chengdu, China.[6]Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, 610041, Chengdu, China.[7]Center of Reproductive Medicine, West China Second University Hospital, Sichuan University, 610041, Chengdu, China.[8]Southwest Medical University, 646000, Luzhou, China.[9]Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, China.四川大学华西医院[10]Analytical & Testing Center, Sichuan University, 610041, Chengdu, China.[11]Chengdu Research Base of Giant Panda Breeding, 610041, Chengdu, China.[12]Auckland University, 1142, Auckland, New Zealand.[13]Teaching Hospital of Chengdu University of TCM, 610041, Chengdu, China.[14]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 650000, Kunming, China.[15]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, China.[16]State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Hospital, Nanjing Medical University, 210029 Nanjing, China
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.
基金：
National Nature Science fund of China
(81370747, 31701085, and 31625015).
第一作者机构：[1]Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, 610041, Chengdu, China.
通讯作者：
通讯机构：[5]Human Sperm Bank, West China Second University Hospital, Sichuan University, 610041, Chengdu, China.[6]Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, 610041, Chengdu, China.[14]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 650000, Kunming, China.[15]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, China.
推荐引用方式(GB/T 7714)：
Shen Ying,Zhang Feng,Li Fuping,et al.Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella[J].NATURE COMMUNICATIONS.2019,10:-.doi:10.1038/s41467-018-08182-x.
APA：
Shen Ying,Zhang Feng,Li Fuping,Jiang Xiaohui,Yang Yihong...&Xu Wenming.(2019).Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella.NATURE COMMUNICATIONS,10,
MLA：
Shen Ying,et al."Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella".NATURE COMMUNICATIONS 10.(2019):-
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