In a new study led by Karolinska Institutet, researchers found that after an egg is fertilized, its surrounding coat tightens, mechanically preventing additional sperm from entering and averting subsequent embryo death. The study also explains how mutations in egg-coat proteins can cause female infertility and may ultimately lead to new contraceptive methods. The study was published in Cell.
Mammalian fertilization begins when a sperm attaches to the egg coat, a fibrous extracellular envelope that it must penetrate to fuse with the egg. An international team has now mapped in detail the structure and function of ZP2, a key component of egg-coat fibers that regulates egg-sperm interactions during fertilization.
“We knew that ZP2 is cleaved after the first sperm enters the egg, and we explain how this event hardens the egg coat and makes it impermeable to other sperm,” said Luca Jovine, professor in the Department of Biosciences and Nutrition at Karolinska Institutet, who led the study. “This prevents polyspermy—the fusion of multiple sperm with one egg—which is fatal to the embryo.”
Changes in the egg coat after fertilization are also essential to female fertility because they protect the developing embryo until implantation in the uterus. This knowledge may help in developing nonhormonal contraceptives that interfere with egg-coat formation. The study also explains forms of female infertility related to the egg coat.
“Mutations in genes encoding egg-coat proteins can cause female infertility, and a growing number of these mutations are being identified,” Luca Jovine explained. “We hope our research can support the diagnosis of female infertility and potentially help prevent unintended pregnancy.”
Importantly, the study also showed that a region of ZP2 previously thought to be a sperm receptor is not required for sperm to attach to the egg. This raises the question of the identity of the true sperm receptor on the egg coat, which the researchers plan to investigate further.
The researchers combined X-ray crystallography and cryo-electron microscopy to study the 3D structure of egg-coat proteins. Functional studies in mice examined interactions between sperm and eggs carrying ZP2 mutations, while the AI program AlphaFold was used to predict the structure of the human egg coat.
The study was conducted with Osaka University and Sophia University in Japan and the University of Pittsburgh in the United States, using data collected at SciLifeLab and the ESRF, DLS and BESSY II synchrotrons.
News | Karolinska Institutet reveals how the egg controls sperm entry
In a new study led by Karolinska Institutet, researchers found that after an egg is fertilized, its surrounding coat tightens, mechanically preventing additional sperm from entering and averting subsequent embryo death. The study also explains how mutations in egg-coat proteins can cause female infertility and may ultimately lead to new contraceptive methods. The study was published in Cell.
Mammalian fertilization begins when a sperm attaches to the egg coat, a fibrous extracellular envelope that it must penetrate to fuse with the egg. An international team has now mapped in detail the structure and function of ZP2, a key component of egg-coat fibers that regulates egg-sperm interactions during fertilization.
“We knew that ZP2 is cleaved after the first sperm enters the egg, and we explain how this event hardens the egg coat and makes it impermeable to other sperm,” said Luca Jovine, professor in the Department of Biosciences and Nutrition at Karolinska Institutet, who led the study. “This prevents polyspermy—the fusion of multiple sperm with one egg—which is fatal to the embryo.”
Changes in the egg coat after fertilization are also essential to female fertility because they protect the developing embryo until implantation in the uterus. This knowledge may help in developing nonhormonal contraceptives that interfere with egg-coat formation. The study also explains forms of female infertility related to the egg coat.
“Mutations in genes encoding egg-coat proteins can cause female infertility, and a growing number of these mutations are being identified,” Luca Jovine explained. “We hope our research can support the diagnosis of female infertility and potentially help prevent unintended pregnancy.”
Importantly, the study also showed that a region of ZP2 previously thought to be a sperm receptor is not required for sperm to attach to the egg. This raises the question of the identity of the true sperm receptor on the egg coat, which the researchers plan to investigate further.
The researchers combined X-ray crystallography and cryo-electron microscopy to study the 3D structure of egg-coat proteins. Functional studies in mice examined interactions between sperm and eggs carrying ZP2 mutations, while the AI program AlphaFold was used to predict the structure of the human egg coat.
The study was conducted with Osaka University and Sophia University in Japan and the University of Pittsburgh in the United States, using data collected at SciLifeLab and the ESRF, DLS and BESSY II synchrotrons.
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