期刊
TOXICOLOGICAL SCIENCES
卷 119, 期 1, 页码 209-217出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfq319
关键词
bisphenol A; steroidogenesis; ovary; antral follicle growth; StAR; pregnenolone
类别
资金
- National Institute of Health [R01 ES019178, P20 ES 018163]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P20ES018163, R01ES019178] Funding Source: NIH RePORTER
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.
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