Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA.
Toxicol Appl Pharmacol. 2010 Dec 1;249(2):107-13. doi: 10.1016/j.taap.2010.09.001. Epub 2010 Sep 16.
Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17β-estradiol (E₂) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 μg/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OH treatment (10 μg/mL) decreased E(2) (DMSO: 3009.72±744.99 ng/mL; mono-OH 0.1 μg/mL: 1679.66±461.99 ng/mL; 1 μg/mL: 1752.72±532.41 ng/mL; 10 μg/mL: 45.89±33.83 ng/mL), testosterone (DMSO: 15.43±2.86 ng/mL; mono-OH 0.1μg/mL: 17.17±4.71 ng/mL; 1 μg/mL: 13.64±3.53 ng/mL; 10 μg/mL: 1.29±0.23 ng/mL), androstenedione (DMSO: 1.92±0.34 ng/mL; mono-OH 0.1 μg/mL: 1.49±0.43ng/mL; 1 μg/mL: 0.64±0.31 ng/mL; 10 μg/mL: 0.12±0.06 ng/mL) and progesterone (DMSO: 24.11±4.21 ng/mL; mono-OH 0.1μg/mL: 26.77±4.41 ng/mL; 1 μg/mL: 20.90±3.75 ng/mL; 10 μg/mL: 9.44±2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.
甲氧滴滴涕（MXC）是一种有机氯农药，通过减少窦卵泡数量和增加卵泡死亡来降低雌性啮齿动物的生育能力。MXC 在体内代谢为单羟基 MXC（单-OH）。关于单-OH 对卵巢的影响知之甚少。因此，这项工作检验了单-OH 暴露会降低培养的小鼠窦卵泡产生 17β-雌二醇（E₂）的假设。窦卵泡从 CD-1 小鼠（35-39 天大）中分离出来，并分别用二甲基亚砜（DMSO）或单-OH（0.1-10μg/mL）处理 96 小时。收集培养基和卵泡进行性激素水平和 mRNA 表达分析。单-OH 处理（10μg/mL）降低了 E₂（DMSO：3009.72±744.99ng/mL；单-OH 0.1μg/mL：1679.66±461.99ng/mL；1μg/mL：1752.72±532.41ng/mL；10μg/mL：45.89±33.83ng/mL）、睾酮（DMSO：15.43±2.86ng/mL；单-OH 0.1μg/mL：17.17±4.71ng/mL；1μg/mL：13.64±3.53ng/mL；10μg/mL：1.29±0.23ng/mL）、雄烯二酮（DMSO：1.92±0.34ng/mL；单-OH 0.1μg/mL：1.49±0.43ng/mL；1μg/mL：0.64±0.31ng/mL；10μg/mL：0.12±0.06ng/mL）和孕酮（DMSO：24.11±4.21ng/mL；单-OH 0.1μg/mL：26.77±4.41ng/mL；1μg/mL：20.90±3.75ng/mL；10μg/mL：9.44±2.97ng/mL）水平。单-OH 没有改变 Star、Hsd3b1、Hsd17b1 和 Cyp1b1 的表达，但它确实降低了 Cyp11a1、Cyp17a1 和 Cyp19a1 mRNA 的水平。总的来说，这些数据表明单-OH 显著降低了关键性激素和类固醇生成所需酶的表达。
