Hormonal control of follicular development and differentiation in mares

为继续开展一项积极和成功的研究计划，以了解母马卵巢卵泡发育和分化的生殖生物学，需要资金。发生在卵巢卵泡中的剧烈生物学变化包括卵泡中产生雌激素的细胞向黄体分泌黄体酮的细胞重新编程。这些对受精和早期妊娠的成功至关重要。本研究计划的长期目标是确定调节马卵泡末期发育、卵泡排卵和卵泡细胞排卵后分化的分子机制。在接下来的五年里，我们建议关注这一发育连续体的三个具体方面：1)了解卵泡黄体生成化过程中卵巢对特定类固醇合成酶的调节，包括那些参与中间雄激素和雌激素产生的酶，17ß羟类固醇脱氢酶（17ß hsd）存在于几种亚型中；2)通过对马排卵泡内硫代偶联过程的研究，探讨类固醇在卵巢内的调节和转运；3)通过阐明包括核受体NR5A2在内的特化核蛋白的作用，研究类固醇合成和排卵基因的转录机制。独特的马模型将解决使用最先进的细胞和分子生物学工具。如果时间和资源允许，我们将扩大研究范围，包括其他过程和候选基因，包括卵巢细胞分化过程中调节组织重塑的基因。研究结果将为人们对马的生殖过程知之甚少提供新的见解，并为更好地管理这一重要经济物种的生殖提供手段。这一发现将进一步成为了解其他单排卵物种卵巢事件的模型。

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.