Ovarian Primordial Follicle Development

卵巢初级卵泡发育 拟议的研究旨在更好地了解控制 原始卵泡发育这一过程对于建立和维持女性的健康至关重要。 生殖原始卵泡的发育涉及原始卵泡组装的初始事件和原始卵泡的发育。 原始卵泡向初级卵泡转变的后续事件。参与原始卵泡的过程 组装不同于原始卵泡向初级卵泡的转变，两者都将在 提议的研究。局部产生的卵巢物质和激素调节的方式 这些方法特别令人感兴趣。先前的研究和初步研究表明， 原始卵泡发育和随后的卵泡发生的控制似乎是由 涉及卵泡膜细胞、颗粒细胞和卵巢上皮细胞的特异性旁分泌因子的局部产生和作用， 卵母细胞初步研究表明，类固醇激素（即雌激素和孕激素）发挥作用， 在原始卵泡组装的开始中起关键作用。初步研究还表明， 初级卵泡过渡需要卵母细胞、颗粒细胞和 前体卵泡膜细胞，包括kit配体（KL）、碱性成纤维细胞生长因子（bFGF）、白血病抑制因子 因子（LIF）、角质形成细胞生长因子（KGF）和骨形态发生蛋白-4（BMP 4）。“将军 假设测试是激素影响的PARACRINE生长因子 卵巢体细胞和卵母细胞之间介导的相互作用 控制初级卵泡的组装和发育”。激素之间的相互作用 旁分泌生长因子是控制原始卵泡发育的有效机制。是 预计这些细胞相互作用的异常将影响女性生育能力、绝经期的开始， 并促进病理生理学，如卵巢早衰。实验方法包括 具体目的：1）阐明激素和旁分泌生长因子对原始卵泡的调控 组装件. 2)阐明激素和生长因子对原始卵泡向初级卵泡转变的控制。 3)阐明介导原始卵泡发育的特定因子的生理重要性。 这些具体目标的完成将扩展以前的观察，并提供对 生长因子介导的细胞-细胞相互作用调节原始卵泡发育。临界 要检查的发育时期包括原始卵泡组装的诱导和 原始卵泡向初级卵泡过渡。预期特定的细胞-细胞相互作用将改变 在这些发展时期之间。激素对生长因子的不同作用及其相关性 受体在卵泡发育的后期具有关键作用，但在原始卵泡中仍有待确定。 卵泡发育预期观察结果将提供深入了解的分子和细胞控制， 原始卵泡发育 公共卫生相关性：获得的信息将用于了解青春期的开始 和更年期，以及提供深入了解未来的潜在设计的诊断程序， 用于异常卵巢状况如卵巢早衰（POF）和各种形式的 女性不孕症提出的未来实验的一个例子是确定突变是否存在于任何 在当前研究中建立的作为潜在致病因素的生长因子和/或受体库 治疗卵巢早衰等疾病

OVARIAN PRIMORDIAL FOLLICLE DEVELOPMENT The proposed research is directed toward developing a better understanding of the mechanisms that control primordial follicle development. This process is essential for the establishment and maintenance of female reproduction. Primordial follicle development involves the initial event of primordial follicle assembly and the subsequent event of primordial to primary follicle transition. The process involved in primordial follicle assembly is distinct from that of primordial to primary follicle transition and both will be investigated in the proposed research. The manner by which locally produced ovarian substances and hormones regulate these processes are of particular interest. Previous research and preliminary studies have demonstrated that the control of primordial follicle development and subsequent folliculogenesis appears to be mediated by the local production and action of specific paracrine factors involving theca cells, granulosa cells, and the oocyte. Preliminary studies have shown that steroid hormones (i.e. estrogen and progesterone) play a critical role in the onset of primordial follicle assembly. Preliminary studies also demonstrate that primordial to primary follicle transition requires integrated interactions between the oocyte, granulosa cells and precursor theca cells involving kit ligand (KL),basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), keratinocyte growth factor (KGF) and bone morphogenic protein-4 (BMP4). "THE GENERAL HYPOTHESIS TESTED IS THAT HORMONES INFLUENCE THE PARACRINE GROWTH FACTOR MEDIATED INTERACTIONS BETWEEN THE OVARIAN SOMATIC CELLS AND THE OOCYTE TO CONTROL PRIMORDIAL FOLLICLE ASSEMBLY AND DEVELOPMENT". Interactions between hormones and paracrine growth factors provide an efficient mechanism to control primordial follicle development. It is anticipated that abnormalities in these cellular interactions will influence female fertility, menopause onset and promote pathophysiologies such as premature ovarian failure. The experimental approach consists of the following specific aims: 1) Elucidate the hormonal and paracrine growth factor control of primordial follicle assembly. 2) Elucidate the hormonal and growth factor control of the primordial to primary follicle transition. 3) Elucidate the physiological importance of specific factors that mediate primordial follicle development. Completion of these specific aims will extend previous observations and provide insight into the role of growth factor mediated cell-cell interactions in regulating primordial follicle development. The critical developmental periods to be examined include the induction of primordial follicle assembly and the primordial to primary follicle transition. It is anticipated that the specific cell-cell interactions will change between these developmental periods. The differential effects of hormones on growth factors and relevant receptors have a critical role in later stages of follicle development, but remain to be determined in primordial follicle development. Observations are anticipated to provide insight into the molecular and cellular control of primordial follicle development. PUBLIC HEALTH RELEVANCE: The information obtained will be used to understand the onset of puberty and menopause, as well as provide insight into the potential future design of diagnostic procedures and therapeutic treatments for abnormal ovarian conditions such as premature ovarian failure (POF) and forms of female infertility. An example of a future experiment proposed is to determine if mutation(s) exist in any of the repertoire of growth factors and/or receptors established in the current study as potential causal factors for disease states such as premature ovarian failure.