Hormonal control of follicular development and differentiation in mares

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Funds are requested for continuation of an active and successful research program aimed at understanding the reproductive biology of ovarian follicular development and differentiation in the mare.  The dramatic biological changes that occur in the ovarian follicle include reprogramming of the estrogen-producing cells of the follicle to the progesterone-secreting corpus luteum. These are essential for the success of fertilization and early gestation. The long term objective of this research program is to determine the molecular mechanisms regulating the terminal development of the equine ovarian follicle, its ovulation and post-ovulatory differentiation of follicular cells.  During the next five years we propose to focus on three specific aspects of this developmental continuum:  1) understanding the ovarian regulation of  specific steroid synthetic enzymes during follicular luteinization, including those involved in intermediary androgen and estrogen production, the 17ß hydroxysteroid dehydrogenases (17ßHSD) which exist in several isoforms; 2) examination of the regulation and transport of steroids in the ovary by studying the process of sulfoconjugation in equine preovulatory follicles; and 3) investigation of the mechanisms of transcription of steroid-synthetic and ovulatory  genes by elucidation of the role of the specialized nuclear proteins including the nuclear receptor NR5A2.   The unique equine model will be addressed using state-of-the-art cellular and molecular biological tools.  As time and resources permit, we will expand the investigation to include other processes and candidate genes in the mare, including those regulating tissue remodelling during ovarian cell differentiation.  The results will provide novel insight into poorly understood reproductive processes in the mare and provide the means for better management of reproduction in this important economic species.  The findings will be further useful as a model to understand ovarian events in other monovulatory species.