Fam170a, a testis-specific gene, is crucial for male fertility. It is involved in the chromatin remodeling process during spermiogenesis, specifically the histone-to-protamine exchange, which is essential for sperm nuclear condensation [1,2]. Mouse models have been valuable in studying its function.

In gene knockout studies, Fam170a-deficient male mice showed abnormal sperm nuclear morphology, abnormal spermiation, reduced progressive sperm motility, and male infertility, mirroring the low Fam170a transcription levels in infertile men with teratozoospermia. Mechanistically, Fam170a is involved in the histone-to-protamine chromatin remodeling, as it affects core histone removal, transition protein translation and degradation, and protamine incorporation. It also interacts with chromatin remodeling-associated proteins, regulates related gene transcription, and specifically interacts with Usp7 to enhance its deubiquitinating activity on testis-specific histone variants [1]. Meanwhile, Fam170b does not compensate for the absence of Fam170a in male fertility [2].

In conclusion, Fam170a is a key regulator of sperm chromatin remodeling. The study of Fam170a knockout mouse models has revealed its significant role in male fertility, providing insights into the mechanisms underlying male infertility and potential directions for improving human male infertility diagnoses [1,2].

References:

1. Cheng, Jinmei, Gu, Yimin, Wang, Yueming, Li, Yinchuan, Sun, Fei. . Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis. In Nucleic acids research, 53, . doi:10.1093/nar/gkaf023. https://pubmed.ncbi.nlm.nih.gov/39868537/

2. Devlin, Darius J, Nozawa, Kaori, Ikawa, Masahito, Matzuk, Martin M. . Knockout of family with sequence similarity 170 member A (Fam170a) causes male subfertility, while Fam170b is dispensable in mice†. In Biology of reproduction, 103, 205-222. doi:10.1093/biolre/ioaa082. https://pubmed.ncbi.nlm.nih.gov/32588889/