New discovery reveals how the human egg controls sperm entry by modulating the architecture of the egg coat

Good news! Maybe it leads to new and better contraceptives or infertility treatment!

"... Researchers ... have now made a breakthrough in understanding how fertilization in mammals is precisely regulated. They found that immediately after the egg is fertilized by a sperm, the surrounding egg coat tightens, acting as a hard barrier that stops additional sperm. This critical process, detailed for the first time, prevents a potentially lethal state for the embryo — polyspermy. In this state, multiple sperm cells fuse with a single egg and can make it unviable. ..."

From the highlights and abstract:

"Highlights

• Post-fertilization cleavage of zona pellucida (ZP) subunit ZP2 makes it oligomerize

• Premature ZP2 oligomerization causes infertility by impairing sperm penetration of ZP

• A native egg coat fragment structure sheds light on heteromeric ZP filament assembly

• Cleaved ZP2 cross-links ZP filaments to harden the egg coat and prevent polyspermy

Summary

Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N-terminal region (NTR) of glycoprotein ZP2, a major subunit of ZP filaments. ZP2 processing is thought to inactivate sperm binding to the ZP, but its molecular consequences and connection with ZP hardening are unknown. Biochemical and structural studies show that cleavage of ZP2 triggers its oligomerization. Moreover, the structure of a native vertebrate egg coat filament, combined with AlphaFold predictions of human ZP polymers, reveals that two protofilaments consisting of type I (ZP3) and type II (ZP1/ZP2/ZP4) components interlock into a left-handed double helix from which the NTRs of type II subunits protrude. Together, these data suggest that oligomerization of cleaved ZP2 NTRs extensively cross-links ZP filaments, rigidifying the egg coat and making it physically impenetrable to sperm."

P.S. It is very annoying that popular science articles do not reveal the source of their information as happened again here. I made the effort again to find the official news release! This is clearly bad practice!

The human egg locks like Fort Knox after it's fertilized. Scientists finally find out how This research could lead to new non-hormonal contraceptives and other insights into female fertility.

New discovery reveals how the egg controls sperm entry (official news release) After the egg has been fertilized by a sperm, the surrounding egg coat tightens, mechanically preventing the entry of additional sperm and the ensuing death of the embryo. This is according to a new study led by researchers at Karolinska Institutet and published in the journal Cell. The work also explains how mutations in egg coat proteins can cause female infertility and may eventually lead to new contraceptive methods.

ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat (open access)

Graphical abstract (this is a nice one)