TY - JOUR
T1 - Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles
AU - Peretz, Jackye
AU - Flaws, Jodi A.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18. h and 72. h, respectively, compared to controls. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased progesterone levels beginning at 24. h and decreased androstenedione, testosterone, and estradiol levels at 72. h and 96. h compared to controls. Further, after removing BPA from the culture media at 20. h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48. h and 72. h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18. h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24. h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72. h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure.
AB - Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18. h and 72. h, respectively, compared to controls. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased progesterone levels beginning at 24. h and decreased androstenedione, testosterone, and estradiol levels at 72. h and 96. h compared to controls. Further, after removing BPA from the culture media at 20. h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48. h and 72. h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18. h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24. h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72. h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure.
KW - Antral follicle
KW - Bisphenol A
KW - Cyp11a1
KW - Reversible
KW - Steroidogenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=84880617747&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2013.04.028
DO - 10.1016/j.taap.2013.04.028
M3 - Article
C2 - 23707772
AN - SCOPUS:84880617747
SN - 0041-008X
VL - 271
SP - 249
EP - 256
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 2
ER -