Sperm contributions to oocyte activation: more that meets the eye

Abstract

It is well known that for successful fertilization, oocyte activation is required, which involves a signal transduction cascade leading to the conversion of the oocyte to a diploid embryo. During oocyte activation, intracellular calcium levels oscillate repetitively causing exocytosis of cortical granules, the enzymes which the latter contain are released into the perivitelline space, leading to modifications of the zona pellucida (ZP), which prevent the penetration of the ZP by further spermatozoa. The necessary element that initiates oocyte activation is apparently the release of intracellular calcium (Ca(2+)) stored in the endoplasmic reticulum (ER). The exact mechanism via which Ca(2+) is released within the oocyte has not been yet clarified, and has been a matter of an ongoing debate. Today, the sperm factor hypothesis has gained general acceptance, according to which a sperm molecule, either phospholipase C (PLCζ) or a post-acrosomal sheath WW domain-binding protein (PAWP), diffuses into the ooplasm initiating a molecular cascade involving mainly the phosphoinositide pathway. Mounting evidence now indicates that these calcium oscillations are caused by a testis-specific PLC termed PLCζ, released into the oocyte following gamete fusion. Also, recently, PAWP has been proposed as an alternative sperm factor candidate. These different sperm candidates have led to a significant debate. This raises important questions as regards to the relative importance of these two proteins as diagnostic tools in reproductive medicine with therapeutic potential, indicating the need for further research. In the present mini review, the phenomenon of oocyte activation during fertilization as well as the existing controversy will be highlighted and the possible mechanisms that are involved in this process will be discussed. Finally, an explanation of the existing debate will be attempted.

Keywords: Fertilization; Human oocyte activation; PAWP; PLCζ.

Fig. 1

The crossroad of oocyte activation. Either PLCζ or PAWP released from the spermatozoon, as sperm factor (SF), into the ooplasm results in calcium oscillations by different pathways. After hydrolyzing PIP₂, the PLCζ factor generates the IP₃ molecule that binds to the respective receptor, IP₃R. The result of this binding causes calcium release. On the other hand, PAWP seems to bind to oocyte-borne YAP proteins that finally activate the phosphoinositidine signal transduction pathway. The function of both sperm factors leads to the periodically wave-like transient calcium release, which in turn produces the exocytosis of cortical granules that leads to oocyte