The molecular basis of mouse sperm–zona pellucida binding: a still unresolved issue in developmental biology

Abstract

During murine fertilization, sperm bind to the specialized extracellular matrix of the egg, known as the zona pellucida (ZP). This matrix is composed of three major glycoproteins designated ZP1, ZP2, and ZP3. Three models for sperm–ZP binding are now under consideration. The domain-specific model posits that adhesion relies primarily on interactions betweenN-glycans located within the C-terminal domain of ZP3 and a lectin-like egg-binding protein in the sperm plasma membrane. However, this model does not explain recent results obtained in studies withZP2mutmice. In the supramolecular structure model, sperm bind to a three-dimensional zona matrix that depends on the cleavage status of ZP2. This paradigm does not explain the potent inhibitory effect of specific carbohydrate sequences or a C-terminal glycopeptide (gp55) derived from ZP3. Recently,O-glycans linked at Thr155and Thr162of ZP3 were implicated as potential ligands that mediate initial sperm–ZP binding. This novel model will be reviewed. A major challenge is to develop an alternate model for sperm–ZP binding that fits as much of the data as possible. Such a model is presented in this review. This paradigm could explain how the inability to cleaveZP2mutinZP2mutmice could result in continued sperm binding to two-cell stage embryos without the formation of a supramolecular binding complex. These novel insights should guide future experiments that will eventually determine the molecular basis underlying gamete binding in the mouse and other eutherian mammals.