MODELING THE MENOPAUSAL TRANSITION AND MENOPAUSE

模拟更年期过渡和更年期

• 批准号: 7485614
• 负责人: Jay Ross Kaplan
• 金额: $ 51.55万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485614
• 关键词: 4-vinyl-1-cyclohexene dioxide; Accounting; Address; Adult; Affect; Age; American; Androstenedione; Animal Model; Animals; Atherosclerosis; Bone Density; Cardiovascular Diseases; Cause of Death; Cells; Characteristics; Chemicals; Chronic; Chronic Disease; Condition; Consensus; Development; Diabetes Mellitus; Disease; Dose; Early treatment; Estradiol; Estrogens; Exposure to; Extramural Activities; Failure; Fracture; Health; Hilar; Hormonal; Hormonal Change; Hormones; Impaired cognition; Impaired health; Individual; Intervention; Invasive; Length; Macaca fascicularis; Malignant Neoplasms; Menopause; Menstrual cycle; Mission; Modeling; Monkeys; Mus; National Institute of Child Health and Human Development; National Institute of Mental Health; Numbers; Occupational; Osteoporosis; Ovarian; Ovarian Tissue; Ovarian hormone; Ovariectomy; Ovary; Perimenopause; Physiological; Population; Postmenopause; Primordial Follicle; Principal Investigator; Procedures; Production; Research; Research Personnel; Residual state; Resources; Risk Factors; Risk Marker; Scientist; Selective Estrogen Receptor Modulators; Sexual Dysfunction; Techniques; Testosterone; Therapeutic Intervention; Time; Woman; aged; clinically relevant; day; design; dietary supplements; disease characteristic; disorder risk; experience; improved; indexing; nonhuman primate; older women; prevent; programs; reproductive; soy

The postmenopausal population of the US is increasing and will comprise 1/3 of all women during the next decade. Cardiovascular disease will be the largest single cause of death in this population, while osteoporosis and resulting fractures will affect up to half of women and many others will suffer from significant cognitive decline. Emerging evidence suggests that these diseases originate premenopausally, especially during the several years ("the perimenopausal transition") that precede menopause and that is characterized byfluctuating - andultimately declining - ovarian hormone production. Nonhuman primates closely resemble women in reproductive characteristics and disease vulnerability. However, while some nonhuman primate species experience menopause, such individuals tend to be aged and are not available in large numbers. As a result, researchers have been limited in their ability to model the pathobiology of the perimenopausal transition and menopause, and to evaluate interventions that might delay or inhibit the development of those diseases that comprise the majority of the postmenopausal health burden in women. The current application is designed to address the foregoing deficiency in menopausal models by exposing cynomolgus monkeys (Macaca fascicularis) to 4-vinylcyclohexene diepoxide (VCD), which selectively destroys ovarian primordial and primary follicles. This approach, developed initially in mice, induces a gradual ovarian failure and results in a follicle depleted animal that retains residual ovarian tissue and that displays a hormone profile similar to that of menopausal women. The four primary aims of the this project are to: 1) determine the VCD exposure that will sufficiently reduce primary and primordial follicles to a level that induces gradual ovarian failure; 2) determine the length of time required for complete ovarian failure (menopause) and define the hormone characteristics of this perimenopausal transition and subsequent menopause; 3) characterize changes in risk markers for chronic disease (atherosclerosis, osteoporosis); and 4) establish a resource for extramural investigators of ovary-intact, follicle-depleted monkeys that can be used in studies focused on menopausal health. This model will thus facilitate research on the major peri- and postmenopausal health concerns, including cardiovascular disease, osteoporosis, diabetes, cognitive decline, sexual dysfunction, and reproductive tract cancers. Therefore the proposed program is directly relevant to the missions of multiple NIHInstitutes, including - butnot limited to - NIA, NICHD, NHLBI, NIDDKand NIMH.

美国的绝经后人口正在增加，下一位妇女的1/3 十年。心血管疾病将是该人群中最大的单一死亡原因，而 骨质疏松症和导致的骨折将影响多达一半的妇女，许多其他妇女将遭受 认知能力大幅下降。新兴的证据表明，这些疾病以绝经前起源于 特别是在更年期之前的几年 表征了偏裂的特征 - 卵巢激素的产生。非人类灵长类动物 在生殖特征和疾病脆弱性上与女性紧密相似。但是，有些 非人类的灵长类动物经历了更年期，这些人往往会老化并且无法使用 大量。结果，研究人员的模拟能力受到限制 围绝经期过渡和更年期，并评估可能延迟或抑制的干预措施 这些疾病的发展包括大多数妇女绝经后健康负担。 当前的应用程序旨在通过暴露于更年期模型的上述缺陷 cynomolgus猴子（Macaca fascicularis）到4-乙烯基环己烯二氧化碳（VCD） 破坏卵巢原始和原发性卵泡。最初在小鼠中开发的方法诱导了 逐渐卵巢衰竭并导致卵泡耗尽的动物，该动物保留了残留的卵巢组织，并且 显示一种类似于更年期女性的激素特征。该项目的四个主要目标 为：1）确定将充分降低主要卵泡和原始卵泡的VCD暴露 这会导致逐渐的卵巢衰竭； 2）确定完全卵巢故障所需的时间长度 （更年期）并定义了这种围绝经期过渡的激素特征和随后的激素特征 绝经; 3）表征慢性疾病的风险标记变化（动脉粥样硬化，骨质疏松症）； 4）为卵泡卵泡，消耗的猴子的壁外研究人员建立资源 用于重点是更年期健康的研究。因此，该模型将促进对主要周期的研究 和绝经后健康问题，包括心血管疾病，骨质疏松症，糖尿病，认知 衰落，性功能障碍和生殖道癌。因此，建议的程序直接 与多个nihinstituts的任务相关，包括 - 不限于-nia，nichd，nhlbi， niddkand nimh。

项目成果

Multidetector computed tomographic morphology of ovaries in cynomolgus macaques (Macaca fascicularis).

食蟹猴（Macaca fasciculis）卵巢的多探测器计算机断层形态。

• 发表时间: 2007
• 期刊: Journal of the American Association for Laboratory Animal Science : JAALAS
• 作者: Jones,JerylC;Appt,SusanE;Bourland,JDaniel;Hoyer,PatriciaB;Clarkson,ThomasB;Kaplan,JayR
• 通讯作者: Kaplan,JayR

Validation of multi-detector computed tomography as a non-invasive method for measuring ovarian volume in macaques (Macaca fascicularis).

验证多探测器计算机断层扫描作为测量猕猴（Macaca fasciculis）卵巢体积的非侵入性方法。

• DOI: 10.1002/ajp.20807
• 发表时间: 2010
• 期刊: American journal of primatology
• 影响因子: 2.4
• 作者: Jones,JerylC;Appt,SusanE;Werre,StephenR;Tan,JoshuaC;Kaplan,JayR
• 通讯作者: Kaplan,JayR