PREGNANCY AND PARTURITION

怀孕和分娩

• 批准号: 3327122
• 负责人: LAIRD WILSON
• 金额: $ 21.62万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3327122
• 关键词: aromatase; baboons; birth; blood chemistry; circadian rhythms; enzyme inhibitors; estradiol; hormone biosynthesis; hormone receptor; hormone regulation /control mechanism; muscle contraction; oxytocin; pregnancy; premature labor; progesterone; radioimmunoassay; uterus

This proposal will test the hypothesis that: (1) the forward shift in the initiation of the nocturnal estradiol (E) surge induces biochemical alterations that initiate nocturnal uterine activity and generates molecular messages that are the genesis of labor and delivery in the baboon; (2) the ratio of E/P is important in determining the time of delivery in the baboon. A tethered baboon model will be used to test these hypotheses. Hypothesis one will be tested by: (1) performing a detailed analysis of the relationship among E, progesterone (P), oxytocin (OT) and uterine contraction by frequent (hourly) blood sampling during the critical 1500 to 2400 hours starting at day 140 of pregnancy through delivery; (2) mimic the shift in the estradiol surge by infusing E for 6 hours starting at 1400 hours on day 140 of pregnancy and monitoring plasma E, P and OT changes and uterine activity during the subsequent 3 days; (3) inhibit E synthesis with 40H androstenedione and CGS 16949 and follow the changes in uterine activity, E, P and OT levels; (4) test the tocolytic effects and monitor plasma OT levels in E treated animals administered an oxytocin antagonist; (5) determine the effects of E on uterine sensitivity to OT and to OT receptor number and affinity. The second hypothesis will be tested by: (1) infusing E intra-arterially daily from 1400 to 2000 hours starting on day 150 of pregnancy and monitoring the initiation of nocturnal uterine activity and-labor compared to control infusions; (2) infusing P, aromatase inhibitor (40HA) and P + 40HA daily from 1400 to 2000 hours starting at day 160 of pregnancy until delivery and compared the initiation of nocturnal uterine activity and delivery to control infusions. The conclusion of these studies will provide significant insights into the factors responsible for the initiation and progress of labor in primates. A better understanding of these factors will provide a basis for determining the causes and providing a treatment of preterm labor, the number one cause of fetal mortality and morbidity in humans.

该提案将检验以下假设：（1） 夜间雌二醇 (E) 激增的开始会诱导生化 启动夜间子宫活动并产生 分子信息是分娩和分娩的起源 狒狒; (2) E/P的比值对于确定时间很重要 狒狒分娩。 拴系狒狒模型将用于测试 这些假设。 假设一将通过以下方式进行检验：（1）执行 E、孕酮（P）、催产素关系详解 (OT) 和通过频繁（每小时）抽血进行子宫收缩 从怀孕第 140 天开始至 1500 至 2400 小时至关重要 送货; (2) 通过输注 E 6 次来模拟雌二醇激增的变化 从怀孕第 140 天 1400 小时开始的小时数和监测 随后 3 天内的血浆 E、P 和 OT 变化以及子宫活动 天; (3)用40H雄烯二酮和CGS 16949抑制E合成，并且 跟踪子宫活动、E、P 和 OT 水平的变化； (4) 测试 E 治疗动物的宫缩效应并监测血浆 OT 水平 给予催产素拮抗剂； (5) 确定E对的影响 子宫对 OT 以及 OT 受体数量和亲和力的敏感性。 这 第二个假设将通过以下方式进行检验：(1) 动脉内输注 E 从怀孕第 150 天开始，每天 1400 至 2000 小时， 监测夜间子宫活动和分娩的开始 与对照输注相比； (2)输注P、芳香酶抑制剂(40HA) 从第 160 天开始，每天 1400 至 2000 小时 P + 40HA 怀孕直至分娩并比较夜间子宫的启动 活性和递送以控制输注。 这些结论 研究将对造成影响的因素提供重要的见解 用于灵长类动物分娩的启动和进展。 更好的 了解这些因素将为确定 早产的原因并提供治疗，这是首要原因 人类胎儿死亡率和发病率。