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Tanya Hoodbhoy Laboratory of Cellular and Developmental Biology, NIDDK, Building 50, Room 3128, National Institutes of Health, 50 South Drive, MSC 8028, Bethesda, Maryland 20892, USA

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Jurrien Dean Laboratory of Cellular and Developmental Biology, NIDDK, Building 50, Room 3128, National Institutes of Health, 50 South Drive, MSC 8028, Bethesda, Maryland 20892, USA

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The zona pellucida surrounding the egg and pre-implantation embryo is required for in vivo fertility and early development. Explanatory models of sperm–egg recognition need to take into account the ability of sperm to bind to ovulated eggs, but not to two-cell embryos. For the last two decades, investigators have sought to identify an individual protein or carbohydrate side chain as the ‘sperm receptor’. However, recent genetic data in mice are more consistent with the three-dimensional structure of the zona pellucida, rather than a single protein (or carbohydrate), determining sperm binding. The mouse and human zonae pellucidae contain three glycoproteins (ZP1, ZP2, ZP3) and, following fertilization, ZP2 is proteolytically cleaved. The replacement of endogenous mouse proteins with human ZP2, ZP3 or both does not alter taxon specificity of sperm binding or prevent fertility. Surprisingly, human ZP2 is not cleaved following fertilization and intact ZP2 correlates with persistent sperm binding to two-cell embryos. Taken together, these data support a model in which the cleavage status of ZP2 modulates the three-dimensional structure of the zona pellucida and determines whether sperm bind (uncleaved) or do not (cleaved).

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Belinda Yauger Laboratory of Cellular and Developmental Biology, Combined Federal Fellowship in Reproductive Endocrinology and Infertility, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA

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Nathan A Boggs
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Jurrien Dean
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The molecular basis of human fertilization remains enigmatic. Mouse models are often used to study sperm–egg recognition, but the mouse zona pellucida surrounding ovulated eggs contains three proteins (ZP1, ZP2, and ZP3) whereas the human zona contains four (ZP1, ZP2, ZP3, and ZP4). Human sperm are fastidious and recognize human but not mouse eggs. Transgenic mouse lines were established to ascertain whether human ZP4 is the sole determinant of human sperm binding. Human ZP4 expressed in transgenic mice had a molecular mass similar to the range of native protein isoforms and was incorporated into the extracellular zona matrix. Transgenic females were fertile with normal litter sizes. Mouse sperm readily recognized transgenic ovulated eggs, but human sperm did not. We conclude that human ZP4 is not sufficient to support human sperm binding to the zona pellucida in transgenic mice and that other zona proteins may be needed for human gamete recognition.

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