Studies on the sperm/oocyte interaction in fertilization

受精的哺乳动物精子穿透透明带，透明带是卵母细胞周围的细胞外基质，融合两种细胞的质膜。精子顶体反应的结果是顶体成分被释放，并与透明带相互作用，这是一个普遍的概念。顶体酶是一种具有胰酶样切割特异性的内切酶，定位于顶体基质中，是一种酶失活的酶原，即原顶体酶。长期以来，顶体酶的生理功能一直被认为是透明带的有限蛋白质分解，使精子能够穿透到卵母细胞表面。在这里，我们表明，尽管精子中的顶体酶蛋白水解酶活性完全丧失，但顶体酶基因定向突变的纯合子雄性小鼠仍然具有生育能力。体外受精试验显示纯合子小鼠精子穿透透明带的时间延迟。这一延迟可能是由于在体外纯合子小鼠精子中42 kDa丝氨酸蛋白酶的产生受到抑制。因此，顶体酶不是精子穿透透明带所必需的。相反，受精早期顶体酶的功能可能与促进42 kDa类胰酶形成有关，该酶是作用于精子穿透的一种候选蛋白质。

A fertilizing mammalian sperm penetrates into zona pellucida, an extracellular matrix surrounding oocyte, to fuse the plasma membranes of both cells. It is a general concept that as a consequence of acrosome reaction of sperm, the acrosomal components are released, and interact with the zona pellucida. Acrosin, an endoprotease with a trypsin-like cleavage specificity, is localizing in the acrosome matrix as an enzymatically inactive zymogen, proacrosin. The physiological function of acrosin has long been believed to be a limited proteolysis of the zona pellucida, enabling sperm to penetrate to the oocyte surface. Here we show that male mice homozygous for a targeted mutation in the acrosin gene are still fertile in spite of the complete loss of the acrosin protease activity in the sperm. In vitro fertilization test reveals a time delay of the homozygous mouse sperm in penetrating into the zona pellucida. This delay is likely due to the fact that production of a 42-kDa serine protease is suppressed in vitro in the homozygous mouse sperm. Therefore, acrosin is not essential for the penetration of sperm into the zona pellucida. Rather, the function of acrosin in the early stages of fertilization may be implicated in the acceleration of formation of the active 42-kDa trypsin-like protease that is a candidate for the protein acting on the sperm penetration.