How sperm get into the zona

Before fertilization can occur, a sperm has to bind to and bore through the zona pellucida layer that encloses the egg. Avella et al. identify the glycoprotein in the zona pellucida that sperm latch onto.

The zona pellucida protects the egg and the early embryo before implantation. Its structure seems simple—in humans it contains four kinds of glycoproteins, and in mice it only holds three. But researchers haven’t been able to identify the sperm’s binding partner in the layer, although their suspicions have fallen on two of the glycoproteins, ZP2 and ZP3.

Avella et al. engineered mice to produce various combinations of human and mouse zona pellucida glycoproteins. Mouse sperm didn’t bind to the zona pellucida if it was missing ZP2, and female mice lacking the protein were sterile. The researchers also found that sperm couldn’t latch onto eggs if ZP2 was missing part of its N terminus. This result jibes with a previous finding that fertilization triggers the release of an enzyme that cleaves ZP2, thus preventing additional sperm from attaching to the zona pellucida. That cut occurs in ZP2’s N terminus and presumably disrupts the binding site.

The team also tested the binding of human sperm to mouse eggs surrounded by a zona pellucida harboring human glycoproteins. Human sperm adhered to the mouse zona pellucida if it contained human ZP2 but not if it carried human ZP3. An unanswered question is which protein sperm use to grip ZP2.