Ovarian Primordial Follicle Development

卵巢原始卵泡发育

• 批准号: 7570040
• 负责人: MICHAEL K SKINNER
• 金额: $ 22.89万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7570040
• 关键词: Agonist; Apoptosis; Cell Communication; Cells; Development; Diagnostic Procedure; Disease; Estrogens; Event; Feedback; Female; Female infertility; Fertility; Fibroblast Growth Factor 2; Functional disorder; Future; Growth Factor; Hormonal; Hormones; In Vitro; Knockout Mice; Laboratory culture; Maintenance; Mediating; Menopause; Molecular; Mutant Strains Mice; Mutation; Oocytes; Organ Culture Techniques; Ovarian; Physiological; Play; Premature Ovarian Failure; Primordial Follicle; Process; Production; Progesterone; Puberty; Recruitment Activity; Regulation; Reproduction; Research; Research Personnel; Role; Somatic Cell; Staging; Stem Cell Factor; Steroids; Testing; Therapeutic; Transgenic Organisms; bone morphogenic protein; critical developmental period; design; folliculogenesis; granulosa cell; human disease; in vivo; insight; interest; keratinocyte growth factor; leukemia inhibitory factor; mouse model; paracrine; prevent; programs; public health relevance; receptor; research study; steroid hormone; theca cell

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.

卵巢原始卵泡发育 拟议中的研究旨在更好地理解控制 原始卵泡发育。这一过程对女性的建立和维持至关重要。 繁殖。原始卵泡发育涉及原始卵泡组装的初始事件和 原始卵泡向初级卵泡转变的后续事件。原始卵泡的发育过程 组装与原始卵泡到初级卵泡的转变是不同的，这两个过程都将在 拟开展的研究。局部产生的卵巢物质和荷尔蒙调节的方式 这些过程特别有意义。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 局部产生和作用特殊的旁分泌因子，涉及膜细胞、颗粒细胞和 卵母细胞。初步研究表明，类固醇激素(即雌激素和黄体酮)在 在原始卵泡组装开始过程中的关键作用。初步研究还表明，原始的 向初级卵泡的转变需要卵母细胞、颗粒细胞和 含有KIT配体(KL)、碱性成纤维细胞生长因子(BFGF)的前体卵泡膜细胞，抑制白血病 LIF、角质形成细胞生长因子(KGF)和骨形态发生蛋白-4(BMP4)。“将军 经检验的假设是激素影响旁分泌生长因子 卵巢体细胞与卵母细胞之间的相互作用 控制原始卵泡的组装和发育“。激素之间的相互作用 旁分泌生长因子为控制原始卵泡发育提供了有效的机制。它是 预计这些细胞相互作用的异常将影响女性的生育能力，更年期的开始 并促进病理生理，如卵巢早衰。实验方法包括 目的：1)阐明激素和旁分泌生长因子对原始卵泡的调控 集合。2)阐明原始卵泡向初级卵泡转化的激素和生长因子调控。 3)阐明调节原始卵泡发育的特定因子的生理意义。 这些具体目标的完成将扩展之前的观察，并提供对 生长因子在调节原始卵泡发育中的细胞间相互作用。关键人物 要检查的发育阶段包括原始卵泡组装的诱导和 原始卵泡向初级卵泡过渡。预计特定的细胞-细胞相互作用将发生变化 在这些发育期之间。激素对生长因子的不同影响及其相关 受体在卵泡发育的后期阶段起关键作用，但在原始阶段仍有待确定。 卵泡发育。预计观察结果将提供对细胞和分子控制的洞察 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 以及对诊断程序和更年期的潜在未来设计的洞察 卵巢异常情况的治疗，如卵巢早衰(POF)和各种形式的 女性不孕不育。拟议的未来实验的一个例子是确定是否存在突变(S) 目前研究中确定的作为潜在致病因素的生长因子和/或受体 用于卵巢早衰等疾病状态。