Identification of CFAP52 as a novel diagnostic target of male infertility with defects of sperm head-tail connection and flagella development
Hui-Juan Jin,
Tiechao Ruan,
Siyu Dai,
Xin-Yan Geng,
Yihong Yang,
Ying Shen,
Su-Ren Chen
Affiliations
Hui-Juan Jin
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, China
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
Siyu Dai
Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, China
Xin-Yan Geng
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, China
Yihong Yang
Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, China; NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, China
Ying Shen
Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, China
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, College of Life Sciences, Beijing Normal University, Beijing, China
Male infertility is a worldwide population health concern. Asthenoteratozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. No evidence indicates the relevance of CFAP52 mutations to human male infertility. Our whole-exome sequencing identified compound heterozygous mutations in CFAP52 recessively cosegregating with male infertility status in a non-consanguineous Chinese family. Spermatozoa of CFAP52-mutant patient mainly exhibited abnormal head-tail connection and deformed flagella. Cfap52-knockout mice resembled the human infertile phenotype, showing a mixed acephalic spermatozoa syndrome (ASS) and multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. The ultrastructural analyses further revealed a failure of connecting piece formation and a serious disorder of ‘9+2’ axoneme structure. CFAP52 interacts with a head-tail coupling regulator SPATA6 and is essential for its stability. Expression of microtubule inner proteins and radial spoke proteins were reduced after the CFAP52 deficiency. Moreover, CFAP52-associated male infertility in humans and mice could be overcome by intracytoplasmic sperm injection (ICSI). The study reveals a prominent role for CFAP52 in sperm development, suggesting that CFAP52 might be a novel diagnostic target for male infertility with defects of sperm head-tail connection and flagella development
