Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Reprod Toxicol. 2012 Jun;33(3):353-60. doi: 10.1016/j.reprotox.2012.01.007. Epub 2012 Jan 28.
Methoxychlor (MXC) and its metabolites bind to estrogen receptors (ESRs) and increase ovarian atresia. To test whether ESR alpha (ESR1) overexpressing (ESR1 OE) antral follicles are more sensitive to atresia compared to controls, we cultured antral follicles with vehicle, MXC (1-100 μg/ml) or metabolites (0.1-10 μg/ml). Results indicate that MXC and its metabolites significantly increase atresia in ESR1 OE antral follicles at lower doses compared to controls. Activity of pro-apoptotic factor caspase-3/7 was significantly higher in ESR1 OE treated antral follicles compared to controls. ESR1 OE mice dosed with MXC 64 mg/kg/day had an increased percentage of atretic antral follicles compared to controls. Furthermore, pro-caspase-3 levels were found to be significantly lower in ESR1 OE ovaries than controls dosed with MXC 64 mg/kg/day. These data suggest that ESR1 OE ovaries are more sensitive to atresia induced by MXC and its metabolites in vitro and in vivo compared to controls.
甲氧滴滴涕（MXC）及其代谢物与雌激素受体（ESR）结合，增加卵巢闭锁。为了测试与对照相比，过表达雌激素受体α（ESR1）的腔前卵泡对闭锁是否更敏感，我们用载体、MXC（1-100μg/ml）或代谢物（0.1-10μg/ml）培养腔前卵泡。结果表明，与对照相比，MXC 及其代谢物在较低剂量下显著增加了 ESR1 OE 腔前卵泡的闭锁。与对照相比，在 ESR1 OE 处理的腔前卵泡中，促凋亡因子半胱天冬酶-3/7 的活性明显更高。与对照相比，接受 MXC 64mg/kg/天剂量的 ESR1 OE 小鼠的闭锁腔前卵泡比例增加。此外，与接受 MXC 64mg/kg/天剂量的对照相比，ESR1 OE 卵巢中的前半胱天冬酶-3 水平明显降低。这些数据表明，与对照相比，ESR1 OE 卵巢对 MXC 及其代谢物在体外和体内诱导的闭锁更为敏感。
