Aging of the Male Reproductive System in Mice

小鼠雄性生殖系统的衰老

• 批准号: 9004806
• 负责人: Frederick vom Saal
• 金额: $ 16.58万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9004806&HistoricalAwards=false
• 关键词: Aging; Male; Reproductive; System; Mice

Dr. Vom Saal will use two research strategies to examine the hypothesis that the levels of sex steroids to which male mice (Mus musculus domesticus) are exposed during fetal life play a major role in influencing aging, particularly of the reproductive system. The first approach involves using a naturally-occurring phenomenon, the intrauterine position phenomenon. Males occupying different intrauterine positions are naturally exposed to different endogenous blood steroid levels during fetal life due to being randomly positioned in utero between 2 male fetuses (these males have elevated serum levels of testosterone) or between 2 female fetuses (these males have elevated serum levels of estradiol). The intrauterine position of males will be identified at cesarean delivery, and they will be raised for examination during later life. The second approach will involve treating pregnant females with either estradiol or testosterone to slightly increase serum concentrations of these steroids during sexual differentiation in all male fetuses of treated mothers. He will examine lifespan, the incidence of tumors in old age, fertility (the capacity to successfully mate with females and sire young), and functioning of the prostate and seminal vesicles (as assessed by enzyme activity and capacity to bind hormones) during aging in male mice. During the fetal period of differentiation of the brain and reproductive system, individuals in all mammalian species may be exposed to markedly different levels of sex steroid hormones due to a variety of reasons. While it is known that individual differences in many characteristics relating to reproduction in young-adult animals are determined by levels of sex hormones during fetal life, no one has examined whether lifespan of the pattern of reproductive aging in males might be predicted by fetal sex hormone levels. In most mammalian species, including man, there are a few aged males who retain the capacity to reproduce, while the majority of males become reproductively inactive in old age. The proposed experiments should provide important information concerning why such dramatic differences in reproductive capacity and lifespan are observed between individual males.

沃姆萨尔博士将使用两种研究策略来检验这一假设 雄性小鼠体内的性类固醇水平 在胎儿期暴露的维生素C在 影响衰老，特别是生殖系统。 第一 方法涉及使用自然发生的现象， 宫内定位现象。 男性占据不同的 子宫内的位置自然暴露于不同的内源性 血液类固醇水平在胎儿生命期间由于被随机放置 在2个雄性胎儿之间的子宫内（这些雄性具有升高的血清水平 睾丸激素）或2个女性胎儿之间（这些男性睾丸激素升高 雌二醇的血清水平）。 男性的子宫内位置将是 他们将在分娩时被发现，并将被抚养 在以后的生活中检查。 第二种方法将涉及 用雌二醇或睾酮治疗妊娠女性， 在性生活期间，这些类固醇的血清浓度略有增加 处理母体的所有雄性胎儿中的分化。 他将 检查寿命，老年肿瘤的发病率，生育能力（ 成功地与雌性交配和繁殖后代的能力），以及 前列腺和精囊的功能（通过酶测定） 活性和结合激素的能力）。 在胎儿时期的分化的大脑和 生殖系统，所有哺乳动物物种的个体可能 由于不同的原因，暴露于明显不同水平的性类固醇激素 各种各样的原因。 虽然人们知道， 许多与成年动物生殖有关的特征 是由胎儿期的性激素水平决定的， 研究了生殖老化模式的寿命是否 男性可能通过胎儿性激素水平来预测。 在大多数 哺乳动物物种，包括人类，有一些老年男性谁保留 繁殖能力，而大多数男性成为 在老年时没有生殖活动。拟议的实验应 提供了重要的信息，说明为什么这种巨大的差异 在个体之间观察到生殖能力和寿命 男性。