REGULATION OF GENE EXPRESSION IN THE AGING OVARY

高龄生育率下降已成为一个重要的因素， 生殖医学的问题。 在这方面，雌鼠 为研究生殖衰老提供了一种相关的、实用的模式。 在 大鼠和人类生殖衰老之前是神经内分泌 以及卵巢功能受损， 促性腺激素分泌、卵巢卵泡发育和排卵。 然而，循环促性腺激素水平与 在生殖衰老之前卵巢功能的变化不是 很好理解。因此，拟议的研究旨在探讨 年龄相关的神经内分泌功能变化之间的关系 以及卵巢基因表达和对 周期性中年雌性大鼠的促性腺激素。 具体而言，该提案的目的是： l）检查是否存在继发性FSH峰的延长 在卵泡池减少的大鼠中（完整的中年大鼠和 与完整的年轻女性相比， 女性），并确定继发性FSH激增 基因表达谱和卵巢癌基因表达谱; 2)评估内源性LH的大小之间的关系 和FSH激增，排卵率，以及诱导的卵巢表达 蛋白水解酶介导卵泡破裂， 中青年雌性大鼠; 3)比较卵巢敏感性和最大排卵和蛋白水解 中青年周期性卵巢癌对外源性hCG刺激的反应 大鼠类似地，为了评估卵巢蛋白酶的相对诱导， 通过外源性重组FSH的表达和排卵来确定 年龄相关的排卵反应变化是否特异于LH 刺激. 这些研究的结果将提供有关 神经内分泌系统和卵巢在生殖系统疾病发病中的作用 衰老 此外，与年龄相关的神经内分泌和 卵巢功能的衰老雌性大鼠提供了一个有用的模型， 下丘脑、垂体和卵巢之间的动态相互作用。 最终，希望这些发现可能会导致发展 与人类年龄相关性衰退相关的新临床策略 生殖功能

The decline in fertility with advanced age has emerged as an important issue in reproductive medicine. In this regard, the female rat has provided a relevant and practical modes to study reproductive aging. In the rat and human, reproductive senescence is preceded by neuroendocrine and ovarian impairments which are reflected by altered patterns of gonadotrophin secretion, ovarian follicular development, and ovulation. However, the relationships between circulating gonadotropin levels and changes in ovarian functions preceding reproductive senescence are not well understood. Therefore, the proposed studies are designed to explore the relationships between age-related changes in neuroendocrine function and potential alterations in ovarian gene expression and response to gonadotrophins in regularly cyclic middle-aged female rats. Specifically, the aims of this proposal are: l) To examine whether there is a prolongation of the secondary FSH surge in rats with decreased follicular pools (intact middle-aged rats and hemiox young and middle-aged females, as compared with intact young females), and to determine the relationship between secondary FSH surge profiles and ovarian inhibin gene expression; 2) To assess the relationships between the magnitudes of endogenous LH and FSH surges, ovulation rate, and induced expression of ovarian proteolytic enzymes mediating follicle rupture in regularly cyclic, middle-aged and young female rats; 3) To compare ovarian sensitivity and maximal ovulatory and proteolytic responses to exogenous hCG stimulation in middle-aged and young cyclic rats. Similarly, to assess relative induction of ovarian proteinase expression and ovulation by exogenous recombinant FSH to determine whether age-related changes in ovulatory response are specific to LH stimulation. The findings from these studies will provide new insights regarding the roles of the neuroendocrine system and ovary in the onset of reproductive senescence. Furthermore, age-related changes in neuroendocrine and ovarian function in the aging female rat provide a useful model to study dynamic interactions between hypothalamus, pituitary and ovary. Ultimately, it is hoped that these findings may result in the development of new clinical strategies relevant to age-related declines in human reproductive function.