The mechanism of sperm–egg interaction and the involvement of IZUMO1 in fusion

Abstract

An average human ejaculate contains over 100 million sperm, but only a few succeed in accomplishing the journey to an egg by migration through the female reproductive tract. Among these few sperm, only one participates in fertilization. There might be an ingenious molecular mechanism to ensure that the very best sperm fertilize an egg. However, recent gene disruption experiments in mice have revealed that many factors previously described as important for fertilization are largely dispensable. One could argue that the fertilization mechanism is made robust against gene disruptions. However, this is not likely, as there are already six different gene-disrupted mouse lines (Calmegin, Adam1a, Adam2, Adam3, Ace and Pgap1), all of which result in male sterility. The sperm from these animals are known to have defective zona-binding ability and at the same time lose oviduct-migrating ability. Concerning spermzona binding, the widely accepted involvement of sugar moiety on zona pellucida 3 (ZP3) is indicated to be dispensable by gene disruption experiments. Thus, the landscape of the mechanism of fertilization is revolving considerably. In the sperm-egg fusion process, CD9 on egg and IZUMO1 on sperm have emerged as essential factors. This review focuses on the mechanism of fertilization elucidated by gene-manipulated animals.

CABYR is essential for fibrous sheath integrity and progressive motility in mouse spermatozoa

“…Consistent with this idea, Cabyr-KO spermatozoa can undergo the acrosome reaction (Fig. S1B,C) that is a prerequisite for sperm-oocyte membrane fusion (Inoue et al, 2011a).…”

Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization

“…Interestingly, the only sperm cells that seem to be able to fuse are acrosome-reacted sperm with Izumo1 gathered in the equatorial segment (Satouh et al, 2012), whereas egg Cd9 as well as sperm Izumo1 are able to interact in a cis way (Ellerman et al, 2009;Inoue et al, 2010a): the role of Izumo1 should therefore be to generate direct robust cell adhesion that would trigger a molecular organization suitable for fusion in the contact area of sperm and egg.…”

Oviductal secretion and gamete interaction

“…It has been proposed that the interaction between integrin-like proteins on the oolemma and disintegrins of transmembrane proteins that contains a disintegrin and metalloprotease domain (ADAM), found on the sperm membrane would be involved in the gamete fusion process (Ikawa et al 2010, Inoue et al 2011). However, this idea is mainly supported by results obtained from studies on the fusion of gamete membranes carried out in mouse models.…”