Investigations into mammalian ovarian follicle development and interactions

哺乳动物雌性卵巢是一个异质性器官，包含封闭在复杂结构（卵泡）中的雌性生殖细胞（卵子，卵母细胞），其最终目的是提供能够受精并产生健康后代的卵母细胞。卵泡发育和分化有多个阶段，卵泡在产生成熟卵母细胞之前必须经过这些阶段。通过来自卵巢内或卵巢外的信号，卵泡发育和生长的稳定状态根据生长卵泡的数量和类型建立。但是大多数卵泡在最早的阶段处于休眠状态，等待轮到它们。 早期卵泡发育的机制仍然知之甚少。因此，拟议的研究计划的长期目标是阐明维持稳态卵泡群体的细胞间和卵泡间相互作用的机制。研究将探索转化生长因子-β超家族的生长/抑制因子及其受体在调节卵巢卵泡发育中的作用。这是通过使用体外培养的小鼠卵巢和将小鼠暴露于专门杀死某些阶段卵泡的物质来操纵卵泡数量来实现的。 研究还在检查卵母细胞中哪些酶是活跃的，以维持其健康。 该研究计划将提供对卵巢生理学所涉及的分子信号传导的更深入了解，这将影响我们对生殖生物学的基本概念和我们在临床环境中使用的工具。

The mammalian female ovary is a heterogeneous organ containing the female germ cells (eggs, oocytes) enclosed in complex structures (follicles), whose ultimate purpose is to provide oocytes capable of being fertilized and producing healthy offspring. There are multiple stages of follicle development and differentiation through which ovarian follicles must pass before producing a mature oocyte. Through signals that come from within or outside the ovary, a steady state of follicular development and growth is established with respect to numbers and types of growing follicles. But the majority of follicles stay dormant, in the earliest stages, waiting for their turn. The mechanisms underlying early follicle development remain poorly understood. Thus, the long-term goal of the proposed research program is to elucidate the mechanisms involved in inter-cellular and inter-follicular interactions that maintain steady-state populations of ovarian follicles. Investigations will explore the role(s) of members of the Transforming Growth Factor-beta superfamily of growth/inhibitory factors and their receptors in regulating ovarian follicular development. This is being accomplished by manipulating follicle populations using both mouse ovaries cultured outside the body and exposing mice to things that specifically kill certain stages of ovarian follicles. Studies are also examining which enzymes are active in the oocyte which maintain its health. The research program will provide greater understanding of molecular signaling involved in ovarian physiology, which will impact both our basic concepts of reproductive biology and the tools we have for use in the clinical setting.