FETAL ALCOHOL EFFECTS: TEMPORAL FACTORS IN TERATOGENESIS

胎儿酒精的影响：致畸的时间因素

• 批准号: 3109025
• 负责人: STERLING K CLARREN
• 金额: $ 17.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-29 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109025
• 关键词: Macaca; alcoholic beverage consumption; animal birth weight; animal developmental psychology; blood chemistry; chronic brain damage; cognition disorders; congenital brain disorder; congenital ear disorder; congenital neuromuscular disorder; congenital oral /facial /cranial defect; congenital skeletal disorder; congenital vision disorder; dosage; electron microscopy; ethanol; fetal alcohol syndrome; gestational age; infant animal; mental retardation; mother /embryo /fetus nutrition; neuropsychological tests; neuropsychology; nutrition related tag; postnatal growth disorder; prenatal growth disorder; sex development disorder; teratogens

In a recently completed research study, ethanol was orally administered once per week to gravid pigtailed macaques (M.nemestrina). The results suggested that teratogenic effects in facial form and cognition occurred in exposures of 1.8 gm/kg (yielding peak plasma ethanol concentrations of about 200 mg/dl), and that the alterations were produced in the first six weeks of gestation. These results stimulate two clinical questions concerning the temporal patterns of alcohol consumption that can be effectively studied in this animal model: 1) Can the primate fetus recover from an initial gestational teratogenic exposure to alcohol through later gestational abstinence? This question will be explored by comparing groups of infant animals gestationally exposed to the 1.8 gm/kg ethanol dose for 0, 3, 6, or all (24) weeks in gestation. 2) How does the teratogenic effect of ethanol relate to the relative exposure to ethanol (the area under the metabolic curve), the peak plasma ethanol concentration, and the weekly frequency of ethanol exposures? This question will be examined by comparing groups of infants fetally exposed to the same cumulative weekly relative ethanol exposure as the infants who were fetally exposed to 1.8 gm/kg once per week throughout gestation as above, but scheduled in two different but typical human consumption patterns -- 1.2 gm/kg ethanol given on two consecutive days per week (modeling weekend drinking) or 0.6 gm/kg ethanol daily. Control dams will receive a daily sucrose solution. Infants in all groups in each study will be assessed on the same measures of physical appearance and cognitive function until they are 15 months of age. The results of these studies should provide information for the reasonable identification of human drinking schedules that are high risk to produce infants with birth defects, especially mental retardation.

在最近完成的一项研究中， 每周一次给予妊娠的猪尾猕猴 （M. nemestrina）。 结果提示， 在1.8 gm/kg剂量下， （产生约200 mg/dl的峰值血浆乙醇浓度）， 而这些改动是在1999年的前六周内完成的 怀孕 这些结果引发了两个临床问题 关于饮酒的时间模式， 在这种动物模型中有效地研究：1）灵长类动物能否 胎儿从最初的妊娠致畸暴露中恢复 酒精通过怀孕后的禁欲 这个问题将 通过比较妊娠期的婴儿动物组来探索 暴露于1.8 gm/kg乙醇剂量0、3、6或全部（24）周 在妊娠期。 2)乙醇的致畸作用与 相对暴露于乙醇（代谢下的面积） 曲线）、血浆乙醇浓度峰值和每周 乙醇暴露的频率？ 这个问题将被审查 通过比较胎儿暴露于相同环境中的婴儿组， 累积每周相对乙醇暴露量， 胎仔每周一次暴露于1.8 gm/kg， 怀孕如上所述，但安排在两个不同的，但典型的 人类消费模式-两个人每天摄入1.2克/千克乙醇 每周连续几天（模拟周末饮酒）或0.6 g/kg乙醇。 对照组母鼠将接受每日蔗糖 溶液 将对每项研究中所有组的婴儿进行评估， 同样的身体外观和认知功能的测量 直到15个月大。 这些研究的结果 应提供信息，以合理识别 人类饮酒时间表是高风险生产婴儿 有先天缺陷，尤其是智力迟钝