AB071. The molecular mechanism of acrosome formation and globozoospermia

OBJECTIVE: The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The present study is to review the molecular mechanism of acrosome formation and explore its relationship with globozoospermia METHODS: We reviewed the published papers from PubMed, and also report some research progress of acrosome formation in our laboratory. RESULTS: Acrosome formation can be divided into four stages: Golgi-phase, cap-phase, acrosome-phase and maturation-phase. In the past 10 years, with gene targeting technology, more than ten genes were identified to be related acrosome formation in mice. Those genes include Casein kinase II α´ catalytic subunit (Csnk2a2), HIV-1 Rev-binding protein (Hrb), Golgi-associated PDZ- and coiled-coil motif-containing protein (Gopc), Beta-glucosidase 2 (Gba2), Zona pellucida binding protein 1 (Zpbp1), protein interacting with C kinase 1 (Pick1), heat shock protein 90kDa beta member 1 (Hsp90β1), autophagy-related gene 7 (Atg7), sperm acrosome associated 1 (Spaca1), Dpy-19-like protein 2 (Dpy19l2) and stromal membrane-associated protein 2 (Smap2). Recently, we generated a Ccdc62 knockout mouse model with CRISPR-Cas9 system. A preliminary data showed that the male mice with Ccdc62 knockout were infertile, and 98% of sperm showed abnormal head with very lower motility, which suggested that Ccdc62 played a very important role in mouse acrosome formation. Globozoospermia is a rare type of teratozoospermia accounting for <0.1% of male infertility. It has reported that the mutation of SPATA16, PICK1 and DPY19L2 were related to clinical globozoospermia. CONCLUSIONS: The process of acrosome formation is regulated by multiple genes and its disorder will results in globozoospermia.