Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis

作     者：Jian-Wen Hou Xiao-Liang Li Li Wang Cong-Ling Dai Na Li Xiao-Hui Jiang Yue-Qiu Tan Er-Po Tian Qin-Tong Li Wen-Ming Xu 

作者机构：Department of Obstetrics/GynecologyKey Laboratory of ObstetricGynecologic and Pediatric Diseases and Birth Defects of Ministry of EducationWest China Second University HospitalSichuan UniversityChengdu 610041China Reproductive Medical CenterChengdu Xi'nan Gynecology HospitalChengdu 610041China Reproductive Medical Center of West China Second University HospitalSichuan UniversityChengdu 610041China Reproductive Medical CenterGansu Provincial Maternal and Child-Care HospitalLanzhou 730050China Institute of Reproductive and Stem Cell EngineeringSchool of Basic Medical ScienceCentral South UniversityChangsha 410000China Reproductive and Genetic Hospital of CITIC-XiangyaChangsha 410000China Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Human Sperm BankWest China Second University HospitalSichuan UniversityChengdu 610041China Clinical Research Center for Reproduction and Genetics in Hunan ProvinceChangsha 410000China Department of ObstetricsGynecology and PediatricsWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationSichuan UniversityChengdu 610041China 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2023年第25卷第1期

页      面：58-65页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：support from the National Key Research and Developmental Program of China (No.2018YFC1003603) the National Natural Science Foundation of China (No.81971445) 

主　　题：azoospermia congenital bilateral absence of the vas deferens CFTR mutation male infertility spermatogenesis 

摘      要：Congenital bilateral absence of the vas deferens(CBAVD)is observed in 1%–2%of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator(CFTR)*** is one of the most well-known genes related to male *** frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia(NOA).CFTR mutations are highly polymorphic and have established ethnic *** with F508Del in Caucasians,the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic ***,whether p.G970D participates in male infertility remains ***,a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and *** retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation(4.1%,5/122),excluding polymorphic ***,we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in *** Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli *** spermatocyte GC-2(spd)ts(GC2)Cftr p.G965D cells,RNA splicing variants were detected and CFTR expression decreased,which may contribute to the phenotypes associated with impaired ***,this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.