Work

Loss-of-function mutations in Ccdc113 cause male infertility in both humans and mice

Year: 2026

Type: article

Abstract: Although genetic factors contribute significantly to male infertility, the underlying mechanisms remain incompletely understood. Coiled-coil domain-containing protein 113 ( CCDC113 ) encodes a coiled-coil domain-containing protein critical for the assembly of cilia and flagella. Using whole-exome sequencing, we identified biallelic CCDC113 mutations in two unrelated families affected by oligoasthenoteratozoospermia. The mutations (c.901A>C; p.K301Q and c.404A>C; p.E135A) cosegregated with infertility phenotypes and were associated with defective sperm flagella. Functional analyses demonstrated that these mutations led to less stable CCDC113 protein and severely disrupted axonemal structures in spermatozoa from our three human patients. We generated Ccdc113 knockout mice, which recapitulated the human infertility phenotypes, including abnormal sperm morphology, impaired motility, and defective spermatogenesis. Importantly, one patient achieved successful pregnancy by intracytoplasmic sperm injection, highlighting the translational potential of genetic diagnostics. These findings suggest that CCDC113 is essential for male fertility and contribute to the understanding of the genetic landscape of infertility, offering novel insights into its diagnosis and management.

Source: Asian Journal of Andrology

DOI: 10.4103/aja202585

Authors: Hong-Tao Yu, Fu-Lin Liu, Xiao-Xiao Zhang, Wei Li

Institutions: University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital

Language: English

Topic: Sperm and Testicular Function

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $711