Block to Polyspermy

Polyspermy is fertilisation of a single oocyte by more than one spermatozoon. It is incompatible with normal development. A polyspermic zygote carries an abnormal, excessive chromosome complement and fails to develop normally, generally resulting in very early pregnancy loss. The oocyte has therefore evolved a rapid, highly effective sequence of mechanisms to prevent entry of any spermatozoon beyond the first.

Once ovulated, an oocyte is typically surrounded by a substantial number of spermatozoa that have navigated the female reproductive tract and penetrated the corona radiata. The risk of more than one spermatozoon reaching and attempting to fuse with the oocyte membrane is genuinely significant. Effective prevention of polyspermy is essential to reliable, normal fertilisation.

The block operates in two sequential phases:

• An immediate, rapid but transient electrical block.
• A slower, more definitive and permanent structural block.

Together they close, as quickly and reliably as possible after the first successful fusion event, the small time window in which additional sperm might otherwise achieve fertilisation.

The first, most rapid response occurs within seconds of the initial sperm-oocyte membrane fusion: a rapid depolarisation of the oocyte plasma membrane, altering its electrical potential in a manner believed to transiently prevent fusion of any further spermatozoa with the oocyte membrane.

This fast electrical block is rapid but also transient and, on its own, insufficient to provide a fully reliable, long-term barrier to polyspermy, which is why it is followed by, and superseded by, the slower but far more definitive structural block.

The cortical granule reaction is the central mechanism of the slower, definitive block to polyspermy. Cortical granules are membrane-bound secretory vesicles located immediately beneath the oocyte plasma membrane, in the cortical cytoplasm. They are formed and stored there during earlier oocyte maturation, in preparation for this reaction.

Calcium oscillations triggered within the oocyte by the initial sperm fusion event trigger exocytosis of the cortical granules. Their contents are released into the perivitelline space, the narrow space between the oocyte membrane and the overlying zona pellucida.

The release occurs as a wave, beginning at the point of sperm entry and spreading around the entire circumference of the oocyte. The protective changes are therefore established across the whole oocyte surface, not only at the point of sperm fusion.

The zona reaction is the direct structural consequence of cortical granule release. Enzymes and other proteins released from the cortical granules act on the zona pellucida and modify its glycoprotein structure. This has two critical effects.

• It destroys or alters the sperm-binding glycoprotein receptors on the zona surface. Additional spermatozoa arriving at the zona pellucida can no longer bind to it as the fertilising sperm originally did.
• It causes a generalised hardening of the zona pellucida matrix as a whole. The matrix becomes substantially more resistant to enzymatic digestion by acrosomal enzymes. Any additional sperm that still make contact with the zona cannot penetrate it, even mechanically.

The fast electrical block and the slower, cortical granule-mediated zona reaction together form a highly reliable, rapidly established barrier. No spermatozoon other than the first to achieve fusion can bind to, penetrate, or fuse with the oocyte. Under normal physiological circumstances, only a single sperm nucleus enters the oocyte and contributes genetic material to the zygote.

Failure of this block, resulting in genuine polyspermic fertilisation, is a recognised, though uncommon, cause of an abnormal conceptus. The zygote has an excessive, non-viable chromosome complement. It is one recognised mechanism contributing to some forms of very early, often preclinical, pregnancy loss, alongside the wider range of chromosomal and structural abnormalities that can similarly prevent normal early embryonic development.