FETAL ALCOHOL AND NICOTINE INDUCED GROWTH RETARDATION

胎儿酒精和尼古丁引起的生长迟缓

• 批准号: 2894150
• 负责人: CHARLES R BREESE
• 金额: $ 10.02万
• 依托单位: AUBURN UNIVERSITY AT AUBURN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-21 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2894150
• 关键词: drug interactions; embryo /fetus toxicology; ethanol; fetal alcohol syndrome; genetic regulation; growth hormone releasing hormone; hormone regulation /control mechanism; insulinlike growth factor; laboratory rat; neurotrophic factors; nicotine; organ culture; polymerase chain reaction; postnatal growth disorder; prenatal growth disorder; second messengers; somatotropin

APPLICANT'S ABSTRACT: Fetal alcohol syndrome is a constellation of birth defects caused by maternal alcohol use during pregnancy, and is characterized by intrauterine and postnatal growth deficits, and CNS dysfunctions in the offspring. Tobacco use during pregnancy is also an established cause of fetal growth deficiency, although the toxicological effects of prenatal nicotine exposure on the CNS are not clear. Since tobacco use is highly correlated in women that abuse alcohol during pregnancy, exposure to the combination of these substances may exacerbate the deficiencies associated with alcohol or tobacco use alone. While intrauterine and postnatal growth deficiencies are the most common symptoms of fetal alcohol or tobacco exposure, the cause of these deficiencies unknown. Studies have shown a consistent long-term reduction of insulin-like growth factor-1 (IGF-1), a major mediator of developmental growth, in prenatally ethanol-exposed offspring. The goal of this application is to investigate the actions of in utero ethanol, nicotine, and ethanol/nicotine co-exposure, on the regulation of the IGF and somatotropin gene families, and assess the relationship of changes in tissue and brain IGF and GH regulation, to that of the growth and CNS deficits observed in these offspring. The hypothesis is that fetal exposure to ethanol and nicotine inhibits fetal and neonatal IGF-1 gene expression, thereby reducing tissue availability to IGF-1, and causing or exacerbating the observed growth deficits observed in these offspring. The proposed studies to test this hypothesis include: 1) Examining the effect of fetal ethanol, nicotine and alcohol/nicotine co-exposure, on plasma and somatic tissue specific IGF and GH peptide and gene regulation; 2) Assessing the effect of fetal ethanol and nicotine exposure and co-exposure on changes on CNS neurotrophic expression, with particular emphasis on the IGF and neurotrophic gene families; 3) Examining the specific actions of ethanol and nicotine exposure on growth factor induced cellular function and second messenger systems, in organ culture systems of affected tissues; and 4) Assessing changes in gene expression by differential display PCR, to identify additional candidate genes in these disorders. These studies will provide valuable data which correlate with the endocrine and neuropathological changes seen in fetal alcohol syndrome and smoking in human populations.

申请人摘要：胎儿酒精综合症是一个出生星座 母亲在怀孕期间饮酒造成的缺陷， 以宫内和产后生长缺陷和中枢神经系统为特征 后代的功能障碍。 怀孕期间吸烟也是一种 胎儿生长缺陷的确定原因，尽管毒理学 产前接触尼古丁对中枢神经系统的影响尚不清楚。 自从 吸烟与酗酒的女性高度相关 怀孕期间，接触这些物质的组合可能会加剧 与单独饮酒或吸烟有关的缺陷。 尽管 宫内和产后生长缺陷是最常见的症状 胎儿酒精或烟草暴露，这些缺陷的原因 未知。 研究表明，长期持续减少 胰岛素样生长因子-1 (IGF-1)，发育的主要介质 在产前暴露于乙醇的后代中生长。 此举的目标 应用是研究子宫内乙醇、尼古丁和 乙醇/尼古丁共同暴露对 IGF 和生长激素的调节 基因家族，并评估组织和大脑变化的关系 IGF 和 GH 调节，对观察到的生长和 CNS 缺陷的调节 这些后代。 该假设是胎儿接触乙醇和 尼古丁抑制胎儿和新生儿 IGF-1 基因表达，从而减少 组织对 IGF-1 的可用性，并导致或加剧观察到的 在这些后代中观察到的生长缺陷。 拟议的研究要测试 该假设包括：1）检查胎儿乙醇、尼古丁的影响 和酒精/尼古丁共同暴露，对血浆和体组织特异性 IGF 以及 GH 肽和基因调控； 2) 评估胎儿乙醇的效果 尼古丁暴露和共同暴露对中枢神经系统神经营养变化的影响 表达，特别强调 IGF 和神经营养基因 家庭； 3) 检查乙醇和尼古丁暴露的具体作用 关于生长因子诱导的细胞功能和第二信使系统， 受影响组织的器官培养系统； 4) 评估基因变化 通过差异显示PCR表达，以确定其他候选者 这些疾病的基因。 这些研究将提供有价值的数据 与胎儿的内分泌和神经病理学变化相关 人群中的酒精综合症和吸烟。