AGING FEMALE BABOON AND OVARIAN FUNCTION

雌性狒狒衰老和卵巢功能

• 批准号: 2002480
• 负责人: FIRYAL S KHAN-DAWOOD
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2002480
• 关键词: aging; androstenedione; baboons; binding proteins; biological models; estradiol; estrone; female; female reproductive system; follicle stimulating hormone; histology; hormone binding protein; immunocytochemistry; inhibin; insulinlike growth factor; luteinizing hormone; mathematical model; menopause; menstrual cycle; model design /development; ovary; progesterone; protooncogene; testosterone; tumor suppressor genes

The aim of this proposal is to examine ovarian aging in the baboon (Papio) with the goal of establishing this model for future studies of the premenopausal-menopausal transition. The hypothesis is that the adult female baboon reaches menopause in a physiologically similar manner to the human female. Thus in this pilot proposal baseline data will be obtained to determine if plasma hormone profiles and follicle dynamics in the baboon are similar to the human female. This data will establish whether the baboon can be used in future studies that are not readily feasible in the human. The baboon population to be examined is based at the Southwest Foundation for Biomedical Research (SWFBR). A cohort of pedigreed females will be divided into groups of five according to chronological age representing, i) adults at peak fertility (age 6- 12 years) (Group A) ii) pre-menopausal, (age 13-22 years) (Group B), and iii) menopausal (age 23-30 years) (Group C). Two aims are proposed.Aim 1: Characterization of the menstrual cycle will involve an examination of i) perineal tumescence to determine menstrual cycle length through 10 cycles and ii) hormone profiles (daily samples from two menstrual cycles) which will indicate ovarian-pituitary activity. Thus hormone analyses will include assays of estrone, estradiol, progesterone, testosterone (total and free), androstenedione, luteinizing hormone, follicle stimulating hormone, insulin-like growth factor 1 and insulin-like growth factor 1 binding protein, the two isoforms of inhibin (inhibin-A and inhibin-B) and sex hormone binding globulin (SHBG). Aim 2 i) Characterization of the follicle population using i) histological sections and analysis of the rate of depletion of non-growing and growing follicles by mathematical models, ii) determination of atresia using DNA fragmentation determination in histological sections, and iii) immunohistological localization of bcl-2 and p53, two factors that have opposing actions in the process of apoptosis. Data will be obtained and statistical analysis of each parameter with comparisons between groups will be performed. Preliminary data suggests a close similarity in the process of reproductive senescence between the human female and the baboon. The data will be the basis of future in vivo and in vitro studies. The studies will be integrated with studies of osteoporosis, cardiovascular and psychosocial changes occurring during the premenopausal and post- menopausal years in the baboon, which are ongoing at the SWFBR. Future studies will also examine uterine, adrenal, thyroid, pineal, pituitary and hypothalamic aging.

该提案的目的是检查狒狒的卵巢衰老情况 （Papio）的目标是为未来的研究建立这个模型 绝经前至绝经期的过渡。假设是 成年雌性狒狒在生理上达到更年期 与人类女性类似。因此，在这个试点提案中 将获得基线数据以确定血浆激素是否 狒狒的外形和卵泡动态与狒狒相似 人类女性。该数据将确定狒狒是否可以 用于未来在人类中不太可行的研究。 待检查的狒狒种群位于西南地区 生物医学研究基金会（SWFBR）。一群有血统的人 女性将根据以下情况分为五组 实际年龄代表，i）处于生育高峰期的成年人（6岁- 12 岁）（A 组）ii) 绝经前，（13-22 岁）（组 B) 和 iii) 更年期（23-30 岁）（C 组）。两个目标是 目标 1：月经周期的特征将 包括检查 i) 会阴肿胀以确定 10 个周期的月经周期长度和 ii) 激素概况 （两个月经周期的每日样本）这将表明 卵巢-垂体活动。因此激素分析将包括 雌酮、雌二醇、孕酮、睾酮（总酮和睾酮）的测定 免费），雄烯二酮，黄体生成素，卵泡刺激 激素、胰岛素样生长因子 1 和胰岛素样生长 因子 1 结合蛋白，抑制素的两种亚型（抑制素-A 和抑制素-B）和性激素结合球蛋白（SHBG）。目标 2 i) 使用 i) 组织学表征卵泡群 非生长和消耗率的剖面和分析 通过数学模型生长卵泡，ii) 确定 在组织学中使用 DNA 片段测定闭锁 切片，以及 iii) bcl-2 的免疫组织学定位和 p53，在过程中具有相反作用的两个因素 细胞凋亡。 获取数据并对各参数进行统计分析 将进行组间比较。初步数据 表明生殖过程非常相似 人类女性和狒狒之间的衰老。数据将 成为未来体内和体外研究的基础。研究 将与骨质疏松症、心血管疾病和 绝经前和绝经后发生的心理社会变化 狒狒的更年期，目前正在 SWFBR 进行。 未来的研究还将检查子宫、肾上腺、甲状腺、松果体、 垂体和下丘脑老化。