Identification of CFAP52 as a novel diagnostic target of male infertility with defects of sperm head-tail connection and flagella development.
Elife
; 122023 Dec 21.
Article
in En
| MEDLINE
| ID: mdl-38126872
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Semen
/
Infertility, Male
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Elife
Year:
2023
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido