MECHANISTIC STUDIES OF OVARIAN TOXICITY

在1996年，我们继续研究乙二醇的影响。 单乙醚对卵巢功能的影响。更好地预测潜力 人类健康风险，我们检查了最接近的代谢物的影响 鸡蛋、2-甲氧基乙酸或MAA对人原代培养细胞的影响 黄体细胞。我们发现人类黄体细胞对MAA的反应是 与大鼠黄体相当 细胞的体外反应，并预测这一数据将有助于 确定女性可接受的接触限值。我们还描述了 成年雌性SD大鼠卵巢肿瘤的发生发展 暴露于TCDD(二恶英)，目前正在确定肿瘤 形态和来源，并确定卵巢和这些肿瘤 有一个ah受体。我们还继续在现场检查 BRCA1基因在小鼠卵巢中的表达 表达与激素刺激无关，但依赖于 细胞周期。我们还在开发用于原位杂交的探针 大鼠BRCA1，小鼠和大鼠BRCA2的研究。 最后，我们确定了环氧合酶1和环氧合酶的作用 2(COX-1和COX-2)在卵巢中的表达 酶，并已确定COX2是排卵所必需的 归纳法。

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.