Actl7a deficiency in mice leads to male infertility and fertilization failure

Mutations in the Actl7a gene have been reported to lead to male infertility; however, the detailed mechanism of this phenomenon remains unknown. In this study, we constructed Actl7a gene knockout (KO) mice and found that Actl7a deficiency led to malformed formation of sperm acrosomes, male infertility, fertilization failure during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and reduced sperm–zona pellucida (ZP) binding ability. Moreover, we found that the localization of the zona pellucida binding protein (ZPBP) was altered in the sperm of Actl7a homozygous KO male mice, which may affect the sperm–zona pellucida binding ability. ACTL7A and ZPBP could form complex, which may be involved in acrosomal formation. Further studies found that localization and expression of the PLCZ1 protein were abnormal in misshapen sperm, leading to reduced calcium oscillations in oocytes. Herein, we provide more detailed mechanisms underlining Actl7a deficiency and male infertility. •Knockout of Actl7a in mice leads to abnormal sperm acrosomes, fertilization failure, and male infertility.•The localization of ZPBP in sperms of Actl7a homozygous knockout mice was altered, and ACTL7A can interact with ZPBP that participate in acrosome formation.•Actl7a deficiency causes abnormal localization and expression of PLCZ1 in sperm, leading to an inability to initiate calcium oscillations in oocytes.