DIOXIN EFFECTS ON NEURAL CONTROL OF REPRODUCTION

二恶英对生殖神经控制的影响

• 批准号: 6150722
• 负责人: SANDRA L PETERSEN
• 金额: $ 19.43万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6150722
• 关键词: aromatic hydrocarbon receptor; dioxins; environmental toxicology; estrogen receptors; estrogens; female; fertility; gene expression; gonadotropin releasing factor; histochemistry /cytochemistry; hypothalamic pituitary adrenal axis; implant; in situ hybridization; laboratory rat; luteinizing hormone; neuroendocrine system; neuroregulation; ovariectomy; receptor expression

DESCRIPTION (Adapted from the Investigator's Abstract): The long-term objective of this research is to determine the mechanism(s) by which dioxin like environmental contaminants affect fertility in females. TCDD, a potent dioxin, has long been known to be a reproductive toxin in subhuman primates and rodents; however, little is known about reproductive outcomes in exposed human populations. In order to evaluate possible effects in humans, a goal of this research is to develop and characterize animal models that show decreased fertility as a result of low-level exposure perinatally and/or in adulthood. To address this question, regional distribution of genes encoding the arylhydrocarbon receptor (AhR; R for TCDD) and its companion protein AhR nuclear translocator (Arnt) in brain was examined. Both genes were found to be expressed in brain regions that have estrogen receptors (ER), which play a crucial role in regulating LH release. These data support that TCDD and related chemicals may interfere with neural actions of estrogen (and its induction of ovulation). AhR and Arnt genes were also found to be expressed in ER-containing regions of the hypothalamus of embryos, supporting possible transplacental effects. The working hypothesis is that: TCDD affects fertility by interfering with estrogen-induced hypothalamic/POA events that trigger LHRH, thus LH surge release. A dose-response study will be performed using environmentally-relevant levels of TCDD, to determine whether perinatal, prepubertal and adult exposure inhibit the ability of estrogen to induce LH release. Ovariectomized, estrogen-treated rats will be used to eliminate ovarian effects of TCDD. Other studies will determine whether local microimplants of TCDD affect LH release when placed in the brain structures known to contain both AhR and ER. Finally, a determination as to whether TCDD alters the ability of the pituitary gland to release LH in response to LHRH will be made.

描述（改编自研究者摘要）：长期 本研究的目的是确定二恶英 比如环境污染物会影响女性的生育能力 TCDD，一种有效的 长期以来，二恶英被认为是灵长类动物的生殖毒素 和啮齿动物;然而，很少有人知道生殖结果在暴露 人类种群。 为了评估对人类可能产生的影响， 这项研究的目的是开发和表征动物模型， 由于围产期和/或孕期低水平接触导致生育力下降 成年 为了解决这个问题，基因的区域分布 编码芳香烃受体（AhR; R代表TCDD）及其伴随物 检测脑内AhR核转位蛋白（Arnt）。 两个基因 被发现在有雌激素受体的大脑区域表达 (ER)在调节LH释放中起着至关重要的作用。 这些数据 支持TCDD和相关化学物质可能干扰神经活动， 雌激素（及其诱导排卵）。 AhR和Arnt基因也是 发现表达于下丘脑的ER-含有区域， 胚胎，支持可能的经胎盘效应。 工作假设 TCDD通过干扰雌激素诱导的 下丘脑/POA事件触发LHRH，因此LH激增释放。 一 将使用环境相关水平进行剂量反应研究 的TCDD，以确定是否围产期，青春期前和成人接触 抑制雌激素诱导LH释放的能力。 卵巢切除， 雌激素处理的大鼠将用于消除TCDD对卵巢的影响。 其他研究将确定局部微植入TCDD是否影响LH 当放置在已知含有AhR和 儿 最后，确定TCDD是否改变了 垂体释放LH以响应LHRH。

项目成果

Evidence that GABAergic neurons in the preoptic area of the rat brain are targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin during development.

• DOI: 10.1289/ehp.02110s3369
• 发表时间: 2002-06
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Hays LE;Carpenter CD;Petersen SL
• 通讯作者: Petersen SL