Fusion of Sperm and Oocyte Membranes

Membrane fusion is the step at which the sperm and oocyte, two separate cells, physically merge into a single cell. In the strictest cellular sense, this event constitutes the moment of fertilisation, rather than penetration.

Fusion allows genetic material to be delivered into the oocyte. It also triggers the oocyte's own activation response.

Having crossed the perivitelline space, the sperm head contacts the oocyte plasma membrane. Contact typically occurs at the microvillar region, a specialised area of the oocyte surface. Its microvilli are thought to help capture and bind the sperm head.

Fusion begins at the equatorial segment of the sperm head. This is the region of the inner acrosomal membrane, exposed after the acrosome reaction, that first contacts the oocyte membrane.

Specific membrane proteins on the sperm and oocyte surfaces mediate the initial binding. They also mediate fusion of the two lipid bilayers into a single, continuous membrane.

Once membrane fusion is established, the entire contents of the sperm head are drawn into the oocyte cytoplasm. These include the highly condensed haploid sperm nucleus, the centriole and the mitochondria of the sperm middle piece.

During spermiogenesis, the sperm nucleus is rendered transcriptionally silent and physically protected by replacement of histones with protamines. Within the oocyte cytoplasm it must then decondense. Oocyte-derived histones progressively replace the protamines.

Only then can the paternal chromatin take part in normal cell cycle processes, including DNA replication, required to form the male pronucleus.

Sperm mitochondria enter the oocyte cytoplasm with the nucleus. They are then selectively targeted for degradation within the fertilised oocyte.

This mechanism underlies the observation that mitochondrial DNA inheritance in humans is, for practical purposes, exclusively maternal, despite paternal mitochondria briefly entering the cell at fertilisation.

Fusion of the sperm and oocyte membranes triggers an immediate, localised electrical change in the oocyte plasma membrane, a rapid depolarisation. It occurs within seconds of fusion.

It is believed to be a rapid, initial block to entry by any additional spermatozoon. This block is transient and incomplete. A slower, more definitive block to polyspermy follows over the subsequent minutes.

Sperm-oocyte fusion triggers oocyte activation. This is a coordinated cascade of intracellular changes. It releases the oocyte from its prior state of developmental quiescence and drives it through the remaining steps required to complete fertilisation.

A sperm-derived factor, released into the oocyte cytoplasm upon fusion, triggers activation. It initiates repetitive, oscillating rises in intracellular calcium concentration within the oocyte.

These calcium oscillations are the central signalling event driving essentially every downstream consequence of fertilisation:

• triggering the cortical granule reaction that establishes the block to polyspermy
• driving resumption and completion of the oocyte's arrested second meiotic division
• initiating the broader metabolic reactivation of the oocyte, which supports the zygote's first mitotic division and the beginning of cleavage

Without this calcium-driven activation cascade, even a spermatozoon that has fused with the oocyte membrane does not trigger the full developmental response. Fertilisation does not proceed to completion.