PREGNANCY MAINTENANCE IN THE OBESE

肥胖者的妊娠维持

• 批准号: 3439532
• 负责人: ALICE M CHELICH
• 金额: $ 7.02万
• 依托单位: CHICAGO COLLEGE OF OSTEOPATHIC MEDICINE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3439532
• 关键词: animal colony; blood chemistry; chorionic gonadotropin; diet; endocrine disorder; fertility; hormone regulation /control mechanism; luteinizing hormone; nutrition related tag; obesity; pregnancy loss; progesterone; radioimmunoassay; reproduction; reproductive system disorder

The genetically obese Zucker rat is characterized by multiple metabolic and endocrine abnormalities including reproductive dysfunction. Obese males copulated but less vigorously and less frequently than lean males. Obese females reported to be uniformly sterile, have severely limited reproductive capacity. However, some aspects of reproductive function were found to be less abnormal than previously reported. Pseudopregnancy and the decidual response can be induced in obese females. Obese females also become pregnant following artificial inemination, but pregnancies consistently fail at mid-term with embryo resorption occurring between days 8-14. In pseudopregnant- decidualized rats, regression of decidual tissue occurs prematurely, also between days 8-14. These two phenomena suggest a deficiency of progesterone during this period. Considering that LH is the major luteotrophic hormone during days 8-11 of pregnancy and pseudopregnancy, a deficiency in LH is proposed to explain the apparent inadequate progesterone secretion. This hypothesis will be tested by artificially inseminating obese rats and treating them with hCG, days 8-11 of pregnancy. Pseudopregnant decidualized rats will be similarly treated. An additional group of rats will be food-restricted by pair feeding to lean controls and the effects of food restriction on pregnancy rate and maintenance investigated. Serum progesterone and LH concentrations for days 8-14 of pregnancy and pseudopregnancy will be determined by RIA; some rats will be sacrificed on day 8 and the rest on day 14. Uteri and ovaries, will be examined histologically for functional differences. The data gathered from these experiments is expected to help elucidate the mechanism(s) of reproductive dysfunction in the obese rat, specifically those causing pregnancy failure. Finally, the information will serve as a basis for developing a method of maintaining pregnancy to term. If litters can be produced by matings of homozygous (fa/fa) obese pairs, all of the offspring will be destined to become obese. Matings of heterozygous (Fa/fa) pairs result in only 25% obese offspring, and these offspring are not visibly identifiable before 3-4 weeks of age. The production of entire litters of obese animals will offer a compelling advantage to the study of early factors, even prenatal factors, involved in the etiology of obesity and diabetes, two diseases for which the genetically obese Zucker rat is an animal model.

遗传性肥胖的Zucker大鼠的特征是多个 代谢和内分泌异常，包括生殖 功能障碍 肥胖的雄性交配，但不那么有力， 比瘦的男性更常见 据报道，肥胖女性 都是不育的，繁殖能力非常有限 然而，生殖功能的某些方面被发现， 比以前报道的要少。 伪孕激素和 可在肥胖女性中诱导蜕膜反应。 肥胖 雌性在人工授精后也会怀孕， 但是怀孕在中期总是失败， 吸收发生在第8-14天之间。 假孕- 蜕膜化大鼠，发生蜕膜组织退化 也在第8-14天之间。 这两种现象 表明这一时期孕激素缺乏 考虑到LH是主要的促黄体激素， 妊娠第8-11天和假性妊娠，LH缺乏 是用来解释明显的孕酮不足 分泌物。 这一假设将通过人工来检验 使肥胖大鼠授精并用hCG处理， 怀孕 假孕脱落大鼠也会类似 治疗。 另一组大鼠将通过以下方式限制食物摄入： 对瘦对照的配对饲养以及食物限制对 怀孕率和维护调查。 血清 妊娠第8-14天的孕酮和LH浓度 将通过RIA测定假孕激素;一些大鼠将 在第8天处死，其余在第14天处死。 子宫和卵巢，威尔 组织学检查功能差异。 数据 从这些实验中收集的数据有望有助于阐明 肥胖大鼠生殖功能障碍的机制， 特别是那些导致妊娠失败的。 最后 信息将作为制定方法的基础， 维持妊娠至足月。 如果垃圾可以通过 纯合子（fa/fa）肥胖对的交配，所有的后代 注定会变得肥胖 杂合子交配 (Fa/fa）对只会导致25%的后代肥胖，而这些 后代在3-4周龄之前是不可明显识别的。 的 生产整窝的肥胖动物将提供一个 对早期因素的研究，即使是产前因素， 因素，参与肥胖和糖尿病的病因，两个 遗传肥胖的Zucker大鼠是一种动物 模型