Sperm Acrosome Biogenesis and Function During Fertilization

Over the last decades, acrosomal exocytosis (also called the "acrosome reaction") has been recognized as playing an essential role in fertilization. Secretion of this granule is an absolute requirement for physiological fertilization. In recent years, the study of mammalian acrosomal exocytosis has produced some major advances that challenge the long-held, general paradigms in the field. Principally, the idea that sperm must be acrosome-intact to bind to the zona pellucida of unfertilized eggs, based largely on in vitro fertilization studies of mouse oocytes denuded of the cumulus oophorus, has been overturned by experiments using state-of-the-art imaging of cumulus-intact oocytes and fertilization experiments where eggs were reinseminated by acrosome-reacted sperm recovered from the perivitelline space of zygotes.§From a molecular point of view, acrosome exocytosis is a synchronized and tightly regulated process that is mediated by molecular mechanisms that are homologous to those reported in the secretion of neuroendocrinal cells. Our goal is to provide a broader perspective, focusing on a limited number of important topics that are essential for understanding the molecular mechanisms governing this step of the fertilization process. In this review we will cover: i) the formation of the acrosome during spermatogenesis; ii) the signaling pathways leading to exocytosis including the participation of ion channels, lipids, the fusion machinery proteins and the actin cytoskeleton; iii) the site of acrosomal exocytosis; iv) the use of gene-manipulated animals used to study this process.