On August 12, 2020, the research article of the teams led by Prof. Cao Yunxia from Anhui Medical University and Prof. Zhang Feng from Fudan University, entitled “Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice”, was published on The American Journal of Human Genetics, IF:10.5, fully proving that loss-of-function variants in CFAP58 could lead to the male infertility of humans and mice.
A total of 90 MMAF-affected Han-nationality Chinese men were enrolled in the research, and via whole-exome sequencing (WES) and genetic analysis, the researchers identified 5 individuals with bi-allelic LoF variants in CFAP58, accounting for 5.6% of the cohort. Transmission electron microscopy (TEM) and multiple molecular biological experiments demonstrated that flagellar ultrastructure defects with axonemal and mitochondrial sheath malformations would lead to decreased sperm motility and malformations, causing infertility for males with bi-allelic LoF variants in CFAP58. To further assess the impact of CFAP58 on spermatogenesis and flagellogenesis in mice, the researchers generated Cfap58-KO mice by using CRISPR-Cas9 technology. Experiments proved that Cfap58-KO male mice were completely infertile, presenting severe flagellar defects (short, or bent, etc.) consistent with the sperm phenotypes in MMAF-affected men.
The research was funded by National Nature Science Foundation of China, Anhui Provincial National-guided Technology Project, Nature Science Foundation of Anhui Province, Key Technological Project of Shanghai and National Key Laboratory of Reproductive Medicine, etc. The First Affiliated Hospital of AHMU is the first-author unit as well as the first corresponding organization. Prof. Cao Yunxia and Prof. Zhang Feng are the co-corresponding authors of the article. The co-first authors are Associate Prof. He Xiaojin, Associate Prof. Lyu Mingrong, Ni Xiaoqing (Doctorate) and Li Qiang (Master Degree Candidate) from Anhui Medical University, as well as Liu Chunyu (Doctorate) from Fudan University and Associate Senior Dr. Yang Xiaoyu from The First Affiliated Hospital of Nanjing Medical University.