EARLY ASPECTS OF FOLLICULAR DEVELOPMENT

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The overall goal of this research is to understand the mechanisms that direct the assembly and early growth of the ovarian follicle in rats. The studies described in this proposal address the following fundamental questions concerning the first steps in folliculogenesis: 1) Are theca interna cells developmentally related to granulosa cells or to connective tissue cells? 2) Are theca interna progenitor cells set aside along with granulosa progenitor cell during assembly of primordial follicles or do they arise continuously throughout life after each primordial follicle has begun to grow? 3) What stimulates dormant primordial follicles to begin growth? a) Is this process under regulatory feedback control? b) Is the locus of control at the local, intraovarian level or at the global level? c) Do TGFalpha and TGF beta play a role in arousing dormant follicles? 4) How does the follicular basement membrane expand to accommodate the enormous increase in follicular volume during follicular growth? 5) Which cells are responsible for depositing and maintaining the basal lamina component of the basement membrane? 6) Does the oocyte induce surrounding somatic cells to deposit a basement membrane during ovarian histogenesis? These questions will be addressed with in vivo studies involving retrovirus-mediated gene transfer to trace cell lineages, isografting of embryonic and infant ovaries to the kidney capsules of adult hosts to distinguish between environmental vs. intrinsic regulation, long term- continuous [3H] thymidine infusion to label slowly proliferating cells, and immunohistochemical detection of basement membrane components at both the light and electron microscopic levels. In addition, synthesis of the basement membrane will be studied in vitro.