Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis

Families with sequence similarity 170 members A (Fam170a) deficiency caused abnormal sperm nuclear morphology and male infertility in mice, mirroring the observation of very low Fam170a transcription in sperm of infertile men with teratozoospermia.Fam170a directly interacted with the deubiquitinating enzyme Usp7 and promoted nuclear translocation of Usp7 in elongating sperm by its nuclear localization sequence, enhancing the deubiquitinating activity of Usp7 on testis-specific histone H2A and H2B variants. Collectively, our findings identified Fam170a as a previously unknown key regulator for sperm chromatin remodeling and revealed that histone deubiquitinating modification might also exert an essential role in the histone-to-protamine exchange.