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Sperm capacitation and binding to the zona pellucida

Capacitation is the final step before sperm can fertilise an oocyte (egg cell), when glycoproteins (proteins with sugar chains attached) and cholesterol leave the sperm membrane.

Remember

Capacitation strips glycoproteins and cholesterol off the sperm surface, and that uncovers the receptors sperm need to bind the zona pellucida (the glycoprotein coat around the oocyte).

Capacitation is the final maturation step for sperm, and it takes place in the female reproductive tract. Glycoproteins and cholesterol are removed from the sperm plasma membrane, which also makes the membrane more fluid. Signalling pathways (chemical messages that change how the cell behaves) are activated inside the sperm as well.

Taking the glycoproteins off the surface is what allows sperm to bind to the zona pellucida. They form a coat over the sperm surface and mask the receptors (docking molecules) that recognise the zona pellucida. Once the coat is stripped away, the receptors are uncovered and the sperm can attach to the zona pellucida.

Binding then triggers the acrosome reaction. The acrosome is the enzyme-filled cap over the sperm head, and in the reaction it releases its enzymes to clear a path through the zona pellucida. Capacitation only primes the sperm for this reaction and is separate from it.

The order is capacitation, binding to the zona pellucida, the acrosome reaction, and finally fusion of the sperm and oocyte plasma membranes. Steps in the male tract come earlier than capacitation. For example, sperm gain motility (the ability to swim) in the epididymis (the coiled tube beside the testis), but that does not enable binding to the zona pellucida.

In IVF (in vitro fertilisation), the sperm meet the oocyte in the laboratory, so they never pass through the female tract first. The laboratory therefore treats them in a capacitation medium to imitate the step.

Key facts

Where it happens
the female reproductive tract, as the final maturation step for sperm.
What changes
glycoproteins and cholesterol are removed from the sperm membrane, which exposes the zona pellucida receptors.
Purpose
the sperm can attach to the zona pellucida and then start the acrosome reaction.
Order of events
capacitation, zona pellucida binding, the acrosome reaction, then fusion of the sperm and oocyte membranes.
In IVF
a capacitation medium imitates the step, because the sperm never meet the female reproductive tract first.

Exam traps

  • A gain in sperm membrane cholesterol is the opposite of what capacitation does, because cholesterol leaves the membrane.
  • The release of enzymes from the acrosome does not make zona pellucida binding possible, because it follows binding and capacitation only primes the sperm for it.
  • Fusion of the sperm and oocyte plasma membranes does not make binding possible, because it happens after the sperm has bound to and crossed the zona pellucida.

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Based on 6 SimpleMed+ questions written and peer-reviewed by UK doctors.

Last updated 7 November 2026. For medical education only, not clinical advice.