FOLLICLE SELECTION: A CELL KINETIC STUDY

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The early antral stage is a pivotal point in follicular development in the cyclic rat. Follicles leave this stage by only two paths: some go on to mature in preparation for ovulation; all others degenerate (undergo atresia). Although the FSH surge plays a major role in determining which follicles will ovulate, its precise mechanism of actin remains unclear. The research proposed here will test the hypothesis that high concentrations of FSH are required during the early antral stage of development to initiate differentiation of the granulosa cells. Because the process of differentiation is associated with the end of cell division, the dynamics of cell proliferation should change as the selection process takes place. I will: (1) fully characterize the dynamics of granulosa cell growth using techniques of cell cycle analysis to identify this decision point in follicular development. (2) measure several parameters of granulosa cell proliferation (growth fraction, birth rate, generation time, synchrony) and determine serum FSH concentrations to correlate cyclic variation in FSH secretion with changes in granulosa cell growth rates. (3) experimentally alter endogenous FSH concentrations (with porcine follicular fluid or hemicastration) to directly test the hypothesis that FSH regulates granulosa cell proliferation. These studies will begin to define the precise mechanism by which one follicle is chosen for ovulation while another is relegated to astresia.