A single sperm at the goal, then the egg raises a wall

A single sperm at the goal, then the egg raises a wall

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Just one sperm fertilizes the egg, just one and that’s it. It penetrates the ovule barrier, all others remain outside. But, as everyone knows – if only thanks to an old Woody Allen film – there are many more sperm that participate in that great obstacle course that is fertilization. Now the question is: how does the egg leave out everyone except the first one that gets in? Or, to put it more scientifically, what is the molecular mechanism that prevents polyspermy, that is, the fusion of multiple sperm with a single egg cell, a phenomenon that is fatal for the fetus?

The number is closed

According to one study Published on Cell, the egg controls who enters and who does not by changing the architecture of its ‘shell’, the filamentous extracellular envelope that surrounds it and which is called the zona pellucida, or ZP. In fact, after fertilization by the first spermatozoon, this covering becomes compact, hardens, transforming into an impermeable barrier to all other male gametes that arrive subsequently. And this is how, irreversibly, polyspermy is blocked, and the embryo is allowed to develop.

Fertility

Not only this: the new work, which was conducted by the Karolinska Institutet in Stockholm in collaboration with the universities of Osaka and Sophia in Japan and Pittsburgh in the United States, also says that any mutations affecting the filamentous proteins that constitute the zona pellucida can cause female infertility, and finally, it also suggests that the new findings could pave the way for possible future non-hormonal contraceptive methods.

ZP2

The authors of the study on Cell have mapped the structure and function of ZP2 in every detail. ZP2 is one of the proteins, a glycoprotein specifically, of which the zona pellucida is made. “We knew that immediately after the first sperm enters the egg cell ZP2 is split (separates into two units, ed.),” he said Luca Jovineprofessor of the department of Biosciences and Nutrition at Karolinska Institutet and one of the authors of the work on Cell. Here, “we explain – she added – how this event stiffens the lining of the egg and makes it physically impervious to other spermatozoa”.

The issue of infertility

The events that occur in the zona pellucida protect the fertilized egg until it implants in the uterus where the pregnancy is initiated (fertilization occurs in the fallopian tubes, i.e. downstream of the ovaries and upstream of the uterus). For this reason, the mechanisms described above Cell they are not only able to prevent polyspermy, but add knowledge on female fertility associated with the zona pellucida, and could have implications for the development of future non-hormonal contraceptives, molecules capable of interfering not with the production of eggs, but with the structure of the their ‘shell’.

“Mutations in the genes that code for egg lining proteins – continues Jovine – can cause female infertility, and more and more mutations of this type are being discovered. We hope that our study can contribute to the diagnosis of infertility and , possibly, to the prevention of unwanted pregnancies”.

The receptor

Before this research it was thought that a part of ZP2 acted as a receptor, i.e. an adhesion zone, between egg and sperm. But this study says that in reality this fraction of ZP2 is not necessary for the two gametes to join together and start fertilization. A discovery that reopens the question of what the sperm receptor is on the egg (the real one at this point).

Artificial Intelligence

To study the 3D structure of egg coat proteins, the research authors combined X-ray crystallography and cryo-EM (cryo-electron microscopy). The interaction between sperm and eggs carrying ZP2 mutations was studied in mice, while an artificial intelligence program was used to study the structure of the lining of human eggs.

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