PATHOBIOLOGY OF PARTHENOGENESIS--MOLECULAR CONTROLS

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Parthenogenesis is the biologic phenomenon whereby cell division and differentiation occurs following activation of an unfertilized gamete. This is a novel pathologic event where meiotic cells aberrantly enter mitosis. This process is analagous to neoplastic transformation of germ cells into ovarian teratomas, the most common human germ cell tumor. Parthenotes offer a unique model to study the genetic regulation of cell division; once initiated, they differ from normal cells in timing and synchronization of cyto- and karyo- kinesis. Although several key regulators of the cell cycle have been described, the complete pathways and full spectrum of in vivo interactions have yet to be defined. Furthermore, parthenotes are of particular interest because they integrate in one system the functional elements common to both development and neoplasia. Parthenotes may be generated and manipulated in vitro, facilitating descriptive and functional studies. The aims of experiments described in this proposal are to define the expression of candidate genes involved in parthenogenesis such as cell cycle genes, cellular oncogenes, growth factor genes, and differentiation genes. This area has been unstudied to date. Parthenotes will be generated in vitro for subsequent mRNA analysis by PCR amplification of cDNA. Expression of candidate genes will be correlated to the phenotype of parthenote development. The hypothesis is that post- activation parthenogenic events are controlled by differential regulation of candidate genes as compared to normal embryos.