MATERNAL PROGESTERONE AND FETAL NEURAL DEVELOPMENT

母体黄体酮与胎儿神经发育

• 批准号: 2675696
• 负责人: CHRISTINE K WAGNER
• 金额: $ 7.6万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2675696
• 关键词: autoradiography; behavioral /social science research tag; developmental neurobiology; embryo /fetus drug adverse effect; estrogen receptors; ethology; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; placental transfer; prenatal stress; progesterone; progesterone receptors; receptor expression; sex behavior

This proposal addresses an issue critically important to the study of mental health: the effects of the maternal/fetal interaction on the development of the brain and subsequent adult behavior. Exposure to gonadal steroid hormones during prenatal life has dramatic consequences on the development of the brain and behavior. While the effects of exposure to estrogen and androgens during development are well documented, almost no information exists on the role of progesterone on neural development and behavior. Fetuses are normally exposed to maternal circulating hormones, including progesterone, the levels of which undergo rapid and extreme changes prior to parturition and during lactation. The children of millions of women in the U.S. who were treated with progesterone during pregnancy to prevent miscarriage show a variety of physical, psychological and behavioral effects.Yet, the developmental effects of perinatal exposure to maternal progesterone remains grossly understudied. The main objective of this proposal is to determine whether the uniquely high levels of progesterone in the maternal-circulation during pregnancy and postpartum can alter the steroid sensitivity of the brain of the offspring during development and/or adult life and thereby alter subsequent hormone- dependent behaviors in adulthood. Specific Aim I will examine when during prenatal life the fetal brain first becomes sensitive to progesterone. Using immunocytochemistry it will be determined when neurons in the fetal brain first begin to express nuclear receptors for progesterone and whether progesterone receptor levels are regulated during neural development. Specific Aim II will use steroid hormone autoradiography to verity that radiolabelled progesterone in maternal circulation can cross the placenta and the fetal blood/brain barrier to bind to nuclear steroid receptors within the fetal brain. In addition, the circulating levels of progesterone in fetuses and the source of the progesterone will be examined. Specific Aim III will examine the effects of pre-and postnatal exposure to progesterone from maternal circulation on the display of steroid hormone dependent behaviors in the adult offspring. Specific Aim IV will examine whether perinatal exposure to progesterone can alter the brains sensitivity to steroid hormones during either neural development or adulthood by altering the expression of progesterone and/or estrogen receptors in brain regions known to be the neural targets for progesterone and estrogen action in the display of hormone-dependent behaviors. The results from these experiments will provide insight as to the role of maternal progesterone in the development of the fetal brain and the expression of critical reproductive behaviors in adulthood.

这项建议解决了一个对研究 心理健康：母婴互动对心理健康的影响 大脑的发育和随后的成人行为。暴露于 产前性腺类固醇激素对 大脑和行为的发展。虽然暴露的影响 在发育过程中对雌激素和雄激素的影响几乎是有据可查的 目前还没有关于孕酮在神经发育中的作用的信息 和行为。胎儿通常暴露在母体循环中 包括黄体酮在内的荷尔蒙，其水平经历迅速和 分娩前和哺乳期间的极端变化。的孩子们 在美国，数百万接受黄体酮治疗的女性 预防妊娠流产表现出多种生理、心理 和行为影响。然而，围产期的发育影响 对母体孕激素暴露的研究仍然严重不足。主 这项提案的目标是确定唯一的高 孕期母体循环中的孕酮水平 产后会改变后代大脑对类固醇的敏感性 在发育和/或成年期间，从而改变随后的荷尔蒙- 成年期的依赖行为。我会在什么时候检查具体的目标 出生前，胎儿的大脑首先对黄体酮敏感。 使用免疫细胞化学将确定胎儿中的神经元 大脑首先开始表达孕酮和孕激素的核受体 孕激素受体水平在神经过程中是否受到调节 发展。特定目标II将使用类固醇激素放射自显影 放射性标记孕酮在母体循环中的可及性 胎盘和胎儿血/脑屏障与核类固醇的结合 胎儿大脑中的受体。此外，空气中的循环水平 胎儿的黄体酮和黄体酮的来源将是 检查过了。具体目标三将检查出生前和出生后的影响 暴露于母体循环中的黄体酮 成年后代的类固醇激素依赖行为。特定目标 IV将研究围产期暴露于黄体酮是否会改变 大脑在神经发育过程中对类固醇激素的敏感性 通过改变孕酮和/或雌激素的表达来实现成年期 已知的脑区受体是孕酮的神经靶点 以及雌激素在激素依赖行为表现中的作用。这个 这些实验的结果将为我们深入了解 母体孕酮在胎脑发育中的作用 关键生殖行为在成年期的表现。