DIOXIN EFFECTS ON NEURAL CONTROL OF REPRODUCTION

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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.