Mammalian Gonadogenesis, Folliculogenesis and Fertilization

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The mouse ovary serves as a paradigm for investigating the developmental biology of mammalian gonadogenesis, oogenesis and fertilization. 1. Gonadogenesis: Mouse gestation occurs over 20 days. Germ cells, first detected in the developing embryo 7.5 days post coitus (dpc), migrate from the allantois to the genital ridge. In XX females, the primitive gonad differentiates into a morphologically distinct ovary by 13 dpc. Poly(A+) was purified from female and male genital ridges isolated 12-13 dpc. cDNA libraries have been made for each sex and expressed sequence tags from random clones from each library have been compared to each other and to existing databases. Gonad or sex-specific genes are being molecularly and genetically evaluated. 2. Oogenesis: The zona pellucida, composed of three glycoproteins (ZP1, ZP2, ZP3), is an ovary- specific extracellular matrix that surrounds growing oocytes. We have cloned the three mouse genes and have demonstrated that their coordinate expression is restricted to oocytes. Approximately 200bp upstream of the start of transcription of each of the three zona genes is a binding site for a novel, gonad-specific basic helix-loop-helix transcription factor, FIG (Factor In the Gonad, alpha). The cloning and characterization of the gene encoding FIG has provided insight into the molecular basis for oocyte-specific gene expression. 3. Fertilization: The three zona proteins are secreted and form an extracellular matrix that mediates the relatively species-specific events of fertilization. To assess protein- protein interactions in the assemblage of the zona matrix, we have established in vitro culture systems that express each of the zona proteins and have developed transgenic mice that either lack a particular zona protein or express the human homologue. Breeding studies and in vitro sperm-egg binding studies are being used to investigate the role of individual zona proteins in the assemblage of the zona matrix and to determine the molecular basis for the specificity of fertilization.