MECHANISTIC STUDIES OF OVARIAN TOXICITY

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In 1996 we continued to examined the effects of ethylene glycol monmeethyl ether (EGME) on ovarian function. To better predict potential human health risks, we examined the effects of the proximate metabolite of EGME, 2-methoxy acetic acid or MAA, on primary cultures of human luteal cells. We found that the human luteal cell response to MAA is quite comparable to the rat luteal cell response in vitro, and predicit this data will be used to help determine acceptable exposure limits in women. We have also described the development of ovarian tumors in adult female Sprague-Dawley rats exposed to TCDD (dioxin) and are currently determining the tumor morphology and origin, and determining whether the ovary and these tumors have the Ah receptor. We also continued to examine the in situ expression of BRCA1 in the mouse ovary and have demonstrated that BRCA1 expression is independent of hormonal stimulation, but is dependent on the cell cycle. We are also developing probes for in situ hybridization studies of BRCA1 in the rat, and BRCA2 in the mouse and the rat. Finally, we are defining the role of cyclooxygenase 1 and cycloxygenase 2 (COX 1 and COX 2) in the ovary using the mice defecient in these enzymes and have established that COX2 is necessary for ovulation induction.