Bisphenol A Impairs Follicle Growth, Inhibits Steroidogenesis, and Downregulates Rate-Limiting Enzymes in the Estradiol Biosynthesis Pathway
Bisphenol A Impairs Follicle Growth, Inhibits Steroidogenesis, and Downregulates Rate-Limiting Enzymes in the Estradiol Biosynthesis Pathway
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DOI：
10.1093/toxsci/kfq319
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Flaws, Jodi A.
中科院分区：
文献类型：
--
作者：
Peretz, Jackye;Gupta, Rupesh K.;Flaws, Jodi A.
双酚A（BPA）被用作塑料和环氧树脂的骨架，包括各种食品和饮料容器。在95%的随机尿液样本和成年女性的卵巢卵泡液中也检测到BPA。很少有研究调查BPA对窦卵泡的影响，窦卵泡是性类固醇激素的主要生产者，也是唯一能够排卵的卵泡。因此，本研究验证了出生后BPA暴露抑制窦卵泡生长和类固醇生成的假设。为了检验这一假设，将从32日龄FVB小鼠分离的窦状卵泡与载体对照（二甲基亚砜[DMSO]）、BPA（4.4-440 μ M）、双烯醇酮（10 μ g/ml）、双烯醇酮+ BPA 44 μ M和双烯醇酮+ BPA 440 μ M一起培养。在培养期间，每天测量卵泡的生长。培养后，对培养基进行雌二醇生物合成途径中激素的ELISA，并对卵泡进行类固醇生成酶的定量实时PCR。结果表明，BPA（440 μ M）抑制卵泡生长，而双烯醇酮共处理不能恢复/维持生长。此外，BPA 44和440 μ M抑制孕酮、脱氢表雄酮、雄烯二酮、雌酮、睾酮和雌二醇的产生。与DMSO对照组相比，孕烯醇酮共处理能够增加BPA处理卵泡中的孕烯醇酮、孕酮和脱氢表雄酮的产生，并维持雄烯二酮和雌酮水平，但无法保护睾酮或雌二醇水平。此外，与DMSO对照相比，双烯醇酮不能保护卵泡免受BPA-（44-440 μ M）诱导的类固醇生成酶抑制。总的来说，这些数据表明BPA靶向卵巢中的雌二醇生物合成途径。
Bisphenol A (BPA) is used as the backbone for plastics and epoxy resins, including various food and beverage containers. BPA has also been detected in 95% of random urine samples and ovarian follicular fluid of adult women. Few studies have investigated the effects of BPA on antral follicles, the main producers of sex steroid hormones and the only follicles capable of ovulation. Thus, this study tested the hypothesis that postnatal BPA exposure inhibits antral follicle growth and steroidogenesis. To test this hypothesis, antral follicles isolated from 32-day-old FVB mice were cultured with vehicle control (dimethyl sulfoxide [DMSO]), BPA (4.4-440 mu M), pregnenolone (10 mu g/ml), pregnenolone + BPA 44 mu M, and pregnenolone + BPA 440 mu M. During the culture, follicles were measured for growth daily. After the culture, media was subjected to ELISA for hormones in the estradiol biosynthesis pathway, and follicles were processed for quantitative real-time PCR of steroidogenic enzymes. The results indicate that BPA (440 mu M) inhibits follicle growth and that pregnenolone cotreatment was unable to restore/maintain growth. Furthermore, BPA 44 and 440 mu M inhibit progesterone, dehydroepiandrosterone, androstenedione, estrone, testosterone, and estradiol production. Pregnenolone cotreatment was able to increase production of pregnenolone, progesterone, and dehydroepiandrosterone and maintain androstenedione and estrone levels in BPA-treated follicles compared with DMSO controls but was unable to protect testosterone or estradiol levels. Furthermore, pregnenolone was unable to protect follicles from BPA-(44-440 mu M) induced inhibition of steroidogenic enzymes compared with the DMSO control. Collectively, these data show that BPA targets the estradiol biosynthesis pathway in the ovary.