Cummings A M, Gray L E
Toxicol Appl Pharmacol. 1987 Sep 15;90(2):330-6. doi: 10.1016/0041-008x(87)90340-1.
The pesticide methoxychlor (MXC) is a proestrogen which is metabolized to a compound that has been shown to exhibit estrogenic activity in vivo and in vitro. Following long-term exposure of female rats to MXC, fertility is reduced and fetotoxicity is evident. However, the effects of MXC on several aspects of maternal reproductive physiology, including the decidual cell response (DCR), ovarian weight, serum progesterone levels, and corpora lutea maintenance, have not been previously described. In the present study, the ability of MXC to interfere with progestational events essential for implantation and the maintenance of pregnancy in the rat was investigated. MXC was administered to pseudopregnant rats, decidualization was induced on Day 4, and the DCR and related parameters were evaluated following euthanasia on Day 9. DCR induction during estrone administration served as a positive control. MXC inhibited decidualization in a dose-dependent manner: while 100 mg/kg/day had no effect, doses of 200, 300, 400, and 500 mg/kg/day produced incremental inhibition of the response. No effects of MXC on ovarian weight, serum progesterone levels, or number of corpora lutea were observed. Estrone also inhibited the DCR in a dose-dependent manner. The data suggest that the anti-fertility effect of MXC is mediated by a suppression of decidualization and that such suppression, which is characteristic of estrogenic compounds, is a direct uterine effect. In the DCR model system, the estrogenic activity of MXC is 1/20,000 times the activity of estrone.
杀虫剂甲氧滴滴涕(MXC)是一种前体雌激素,其代谢产物已被证明在体内和体外均具有雌激素活性。雌性大鼠长期接触MXC后,生育能力降低,胎儿毒性明显。然而,此前尚未描述MXC对母体生殖生理学若干方面的影响,包括蜕膜细胞反应(DCR)、卵巢重量、血清孕酮水平和黄体维持。在本研究中,研究了MXC干扰大鼠着床和维持妊娠所必需的孕激素事件的能力。给假孕大鼠施用MXC,在第4天诱导蜕膜化,并在第9天安乐死后评估DCR及相关参数。在施用雌酮期间诱导DCR作为阳性对照。MXC以剂量依赖性方式抑制蜕膜化:虽然100 mg/kg/天没有效果,但200、300、400和500 mg/kg/天的剂量对反应产生逐渐增强的抑制作用。未观察到MXC对卵巢重量、血清孕酮水平或黄体数量有影响。雌酮也以剂量依赖性方式抑制DCR。数据表明,MXC的抗生育作用是通过抑制蜕膜化介导的,这种抑制作用是雌激素化合物的特征,是一种直接的子宫效应。在DCR模型系统中,MXC的雌激素活性是雌酮活性的1/20000倍。