Biogenesis of the Mouse Egg's Extracellular Coat, the Zona Pellucida

Biogenesis of the zona pellucida (ZP), the extracellular coat that surrounds all mammalian eggs, is a universal and essential feature of mammalian oogenesis and reproduction. The mouse egg's ZP consists of only three glycoproteins, called ZP1-3, that are synthesized, secreted, and assembled into an extracellular coat exclusively by growing oocytes during late stages of oogenesis while oocytes are arrested in meiosis. Expression of ZP genes and synthesis of ZP1-3 are gender-specific. Nascent ZP1-3 are synthesized by oocytes as precursor polypeptides that possess several elements necessary for their secretion and assembly into a matrix of long fibrils outside of growing oocytes. Failure to synthesize either ZP2 or ZP3 by homozygous null female mice precludes formation of a ZP during oocyte growth and, due to faulty folliculogenesis and a paucity of ovulated eggs, results in infertility. High-resolution structural analyses suggest that ZP glycoproteins consist largely of immunoglobulin (Ig)-like folds and that the glycoproteins probably arose by duplication of a common Ig-like domain. Mouse ZP1-3 share many features, particularly a ZP domain, with extracellular coat glycoproteins of eggs from other vertebrate and invertebrate animals whose origins date back more than 600 million years. These and other aspects of ZP biogenesis are discussed in this review.