Influence of the zona pellucida of the mouse egg on folliculogenesis and fertility

All mammalian eggs are surrounded by a relatively thick extracellular coat, called the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. The mouse egg ZP consists of three glycoproteins, called mZP1-3, that are syn-thesized solely by oocytes during their 2-to-3 week growth phase. The ZP is seen initially as isolated extracellular deposits of nascent ZP fibrils that coalesce to form a thickening matrix. Elimination of ZP glycoprotein synthesis by targeted mutagenesis yields mice that are hetero-zygous or homozygous for the null mutations. Homozygous null males are unaffected by the mutations and heterozygous females are as fertile as wild-type females. On the other hand, eggs from mZP2-/- and mZP3-/- females lack a ZP and the mice are com-pletely infertile due to a severely reduced number of ovulated eggs in their oviducts. Develop-ment of ovarian follicles is retarded in homozygous null females and manifested as reduced ovarian weight, number of Graafian follicles, and number of ovulated eggs. Eggs from mZP1-/- females have a distorted ZP and, although the mice are fertile, they exhibit re-duced fertility due to early embryonic loss. Potential relationships between ZP biogenesis, folliculogenesis, and fertility are addressed.