This is how the egg protects itself from fertilization by too many sperm

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– It is known that ZP2 is cleaved after the first sperm enters the egg. Now we can show how this event makes the egg shell more rigid and impermeable to other sperm. In this way, polyspermy is prevented, meaning the fusion of several sperm into one egg, which is a fatal condition for the fetus, he says. Luca Goffinprofessor at Department of Life Sciences and NutritionKarolinska Institutet, which led the research.

Changes in eggshells after fertilization are also crucial to a woman's fertility because they protect the growing embryo until it implants in the uterus. Therefore, new knowledge may be important for the development of non-hormonal contraceptives that interfere with egg shell formation. In addition, the study explains infertility in women resulting from changes in the egg shell.

Mutations in the genes that code for egg coat proteins can cause infertility in women, and more and more of these mutations are being discovered. “We hope that our study will facilitate the diagnosis of infertility in women and perhaps also contribute to the prevention of unwanted pregnancies,” says Luca Goffin.

Searching for sperm receptors

The study also shows that part of ZP2 that was previously thought to function as a sperm receptor (receptor) is not necessary for sperm to attach to the egg. This raises the question of what the sperm's actual future is on the egg envelope, something the researchers plan to investigate further.

The researchers combined X-ray crystallography and cryo-electron microscopy to study the 3D structure of eggshell proteins. The interaction between sperm and eggs carrying mutations in the ZP2 protein was studied in mice, while the artificial intelligence program AlphaFold was used to predict the structure of the egg shell in humans.

The study was conducted in collaboration with Osaka University, Sophia University, Japan, and the University of Pittsburgh, USA, using data collected at SciLifeLab and the synchrotrons ESRF, DLS, and BESSY II.

The research was mainly funded by the Knut and Alice Wallenberg Foundation, the Swedish Research Council and the Center for Innovative Medicine (CIMED). There are no reports of conflicts of interest.

Publishing

“ZP2 cleavage prevents polyspermy by modifying the structure of the egg envelope.”Shunsuke Nishio, Chihiro Imori, Benjamin Weissmann, Dirk Vahrenkamp, ​​Elisa DioGuardi, Sara Zamora Caballero, Marcel Bukhoff, Ling Han, Alina Stsiapanava, Blanca Algara, Yonggang Lu, Mayu Kodani, Rachel E. Bainbridge, Kayla M. Komondor, Anne E. Carlson, Michael Landre, Daniel De Sanctis, Shigeki Yasumasu, Masahito Ikawa, Luca Goffin, cellonline 14 March 2024, doi: 10.1016/j.cell.2024.02.013.