Abstract Title:

Bisphenol A impairs follicle growth, inhibits steroidogenesis, and downregulates rate-limiting enzymes in the estradiol biosynthesis pathway.

Abstract Source:

Toxicol Sci. 2010 Oct 18. Epub 2010 Oct 18. PMID: 20956811

Abstract Author(s):

Jackye Peretz, Rupesh K Gupta, Jeffrey Singh, Isabel Hernández-Ochoa, Jodi A Flaws

Article Affiliation:

Jackye Peretz: University of Illinois, Urbana IL, 61802; [email protected].

Abstract:

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 (dimethylsulfoxide; DMSO), BPA (4.4-440μM), pregnenolone (10μg/mL), pregnenolone + BPA 44μM, and pregnenolone + BPA 440μM. During the culture, follicles were measured for growth daily. After the culture, media was subjected to enzyme-linked immunosorbent assays for hormones in the estradiol biosynthesis pathway, and follicles were processed for quantitative real-time polymerase chain reaction of steroidogenic enzymes. The results indicate that BPA (440μM) inhibits follicle growth and that pregnenolone co-treatment was unable to restore/maintain growth. Further, BPA 44μM and 440μM inhibit progesterone, dehydroepiandrosterone,androstenedione, estrone, testosterone, and estradiol production. Pregnenolone co-treatment was able to increase production of pregnenolone, progesterone, and dehydroepiandrosterone and maintain androstenedione and estrone levels in BPA treated follicles compared to DMSO controls, but was unable toprotect testosterone or estradiol levels. Further, pregnenolone was unable to protect follicles from BPA (44- 440μm) induced inhibition of steroidogenic enzymes compared to the DMSO control. Collectively, these data show that BPA targets the estradiol biosynthesis pathway in the ovary.

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