Intrafollicular Mechanisms Regulating Oocyte Maturation
Arrest and reinitiation of oocyte maturation occur in association with the processes of folliculogenesis and ovulation. Somatic cells in the ovarian follicle play important and variable roles in regulating these events. This review considers 2 aspects of somatic cell physiology in relation to maturational events in the ovarian follicle: 1) their endocrine metabolic activity (amphibians) and 2) cell cycle characteristics (mammals). In amphibians reinitation of meiosis following gonadotropin stimulation is linked to intrafollicular production and action of progesterone. Endogenous intrafollicular levels of progesterone fluctuate in response to physiological and experimental treatments. Amphibian gonadotropins (pituitary extracts) stimulate a rapid and progressive increase in intrafollicular levels of progesterone which precedes GVBD during in vitro culture. Subsequently, follicular and oocyte levels of the steroid decline, presumably as a result of its metabolism. Intrafollicular progesterone levels respond to manipulation of endogenous cAMP levels. Coordinated stimulation of adenylate cyclase and inhibition of phosphodiesterase enzymes maximize intrafollicular progesterone levels and replicate the steroidogenic effects of gonadotropins. Less dramatic changes in intrafollicular progesterone levels occur in response to alterations in endogenous and exogenous calcium concentrations. The magnitude of the steroidogenic response of follicles varies depending on the nature of the stimulation. Oocyte maturation is not assured in the presence of elevated intrafollicular levels of steroid and cAMP. Evidence suggests that the relative amounts of cAMP and steroid play key roles in determining whether and when oocyte maturation occurs within ovarian follicles. The pathway for gonadotropin stimulation of progesterone synthesis appears to proceed via cAMP synthesis, cholesterol mobilization and pregnenolone synthesis. Continuous protein synthesis is required for progesterone production and involves early events in the steroidogenic cascade prior to enzymatic conversion of pregnenolone to progesterone. Maturation of oocytes, without evident hormone stimulation, can be achieved in the presence or absence of the somatic cells, following activation of protein kinase C or transient exposure to a synthetic protease inhibitor (TPCK) of chymotrypsin. Results indicate that several pathways exist for regulating arrest and reinitation of meiosis in the germ cell and all are sensitive to inhibition by cAMP. In addition to endocrine changes, somatic granulosa cells (mammals) undergo characteristic changes in their cell cycle profiles in association with follicle growth and ovulation of mature oocytes. The proportion of granulosa cells engaged in DNA synthesis (S-phase of the cell cycle) decreases markedly during the periovulatory period. Results suggest that endocrine and cell cycle changes in somatic cells which occur during follicle and oocyte maturation may be inter-dependent processes and an important area for future research.
KeywordsGranulosa Cell Oocyte Maturation Ovarian Follicle Progesterone Production Rana Pipiens
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