Ovarian Germ and Somatic Cell Function

Theme leader : Dr. Hugh Clarke, McGill University

The problem: The oocyte is the female gamete. It differentiates during prenatal development then arrests at the first meiotic division. This arrest last until a few hours before ovulation in mammals. Female gametogenesis requires a coordinated dialogue between the oocyte and the somatic cells that comprise the ovarian follicle. Indeed the oocyte is in an electrophysiologic syncytium with the cumulus cells and the granulosa. These cells control not only the ovocytic meosis, but also the metabolism, the entry of transduction signal and many more. There is much to learn about these processes, as their pleiotropic dysregulation is a major cause of infertility. During their lifespan, oocytes and follicles are subject to multiple xenobiotic insults, and these, as well as aging, affect viability and fertilization competence.  

Plan: The RQR has a unique, multifaceted capability to address the complexities of ovarian somatic/germ cell interactions and development in multiple models. Chromatin function in oocyte maturation will be addressed, as will DNA methylation status and mechanisms. Innovative investigation of signaling mechanisms by the fluorescence recovery after photobleaching (FRAP) technique, along with investigations of oocyte signal cascades will be undertaken. In the somatic compartment, folliculogenesis will be examined by global transcriptome analysis, and chromatin and epigenetic regulation by global and locus specific analysis of DNA methylation and by studying histone modifications. Signaling in follicle cells will be examined using large animal and transgenic mouse models. Genomic variation will be addressed by interrogation of our unique DNA and phenotypic data banks. As extrinsic factors are important determinants of ovarian function and fertility, the consequences of xenobiotic exposure in rodent models, along with nutritional influences on oocyte maturation, fertilization and consequent embryogenesis in porcine and bovine models will be investigated. This combination of basic, environmental and clinical investigation will provide new insight into ovarian function and the etiology of infertility.


Summary of the 1st theme meeting during the RQR Symposium

Summary of the theme meeting during the 3rd symposium of the RQR (November 17th 2010)