How Does the Egg Coat Prevent Multiple Fertilization

A recent study discovered the mechanism that prevents a second sperm from entering a fertilized egg. The surrounding egg coat tightens once a sperm fertilizes an egg, mechanically blocking further sperm from entering and causing the embryo to die.

Luca Jovine. Image Credit: Bildmakarna

The research was published in the journal Cell. It clarifies how changes in egg coat proteins can result in female infertility and could potentially pave the way for novel forms of birth control.

Mammals begin to fertilize when a sperm clings to the egg coat, an extracellular filamentous barrier that the sperm must pass through to fuse with the egg. The structure and function of the protein ZP2, a component of the egg coat filament that is essential for controlling the interactions between the sperm and the egg during fertilization, have now been thoroughly mapped by an international team of researchers.

A Fatal Condition for the Embryo

It was known that ZP2 is cleaved after the first sperm has entered the egg, and we explain how this event makes the egg coat harder and impermeable to other sperm, and this prevents polyspermy – the fusion of multiple sperm with a single egg – which is a fatal condition for the embryo.”

Luca Jovine, Professor and Study Lead Author, Department of Biosciences and Nutrition, Karolinska Institutet

They guarantee the protection of the developing embryo until it implants in the uterus; the modifications made to the egg coat following fertilization are also essential to female fertility.

Therefore, the new knowledge may affect the development of non-hormonal contraceptives that obstruct the formation of the egg coat. Additionally, the study clarifies forms of female infertility linked to egg coats.

Mutations in the genes encoding egg coat proteins can cause female infertility, and more and more such mutations are being discovered, and we hope that our study will contribute to the diagnosis of female infertility and, possibly, the prevention of unwanted pregnancies.”

Luca Jovine, Professor and Study Lead Author, Department of Biosciences and Nutrition, Karolinska Institutet

Looking for the Sperm Receptor

Crucially, the study also demonstrates that sperm do not need to attach to the egg for a portion of ZP2, which was previously believed to function as a receptor for sperm. The researchers intend to look into this further to determine what the actual sperm receptor on the egg coat is.

The scientists used cryo-EM and X-ray crystallography to investigate the three-dimensional structure of egg coat proteins. While the AI tool AlphaFold was utilized to predict the structure of the human egg coat, functional research was done on the interaction between sperm and eggs containing mutations in the ZP2 protein in mice.

Source:
Journal reference:

‌Nishio, S., et al. (2024) ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat. Cell. doi.org/10.1016/j.cell.2024.02.013.

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