Bisphenol A impairs follicle growth, inhibits steroidogenesis, and downregulates rate-limiting enzymes in the estradiol biosynthesis pathway.
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 (dimethyl sulfoxide [DMSO]), BPA (4.4-440 μM), pregnenolone (10 μg/ml), pregnenolone + BPA 44 μM, and pregnenolone + BPA 440 μM. 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 μM) inhibits follicle growth and that pregnenolone cotreatment was unable to restore/maintain growth. Furthermore, BPA 44 and 440 μM 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 μM) induced inhibition of steroidogenic enzymes compared with the DMSO control. Collectively, these data show that BPA targets the estradiol biosynthesis pathway in the ovary.
Keywords
NMR
HPLC
sodium carboxymethyl cellulose
SEM
metabolic disease
high-performance liquid chromatography
gst
ampk
nox
mtor
traditional chinese medicine
thin layer chromatography
glutathione-s-transferase
nf-κb
mammalian target of rapamycin
nuclear magnetic resonance
dimethyl sulfoxide
fcs
pbs
fetal calf serum
peroxisome proliferator-activated receptor gamma
tlc
bovine serum albumin
dmso
bmp
natural product
bsa
anova
srebp
pparγ
dmem
phosphate buffered saline
lbd
3-isobutyl-1-methylxanthine
amp-activated kinase
atcc
american type culture collection
badge
cmcna
dulbecco's modified eagle's medium
ec(50)
egfp
ibmx
mef
nadph-dependent oxidase
nbs
peroxisome proliferator-activated receptor
rxr
spf
tcm
tr-fret
analysis of variance
bisphenol a diglycidyl ether
bone morphogenic protein 4
effective concentration 50%
enhanced green fluorescent protein
ligand-binding domain
mouse embryonic fibroblasts
newborn bovine serum
nuclear factor κb
retinoic x receptor
specific pathogen free
standard error of the mean
sterol regulatory element binding protein
time-resolved fluorescence resonance energy transfer
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74044
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Article ID:
74044
Unique Identifier:
10.1093/toxsci/kfq319
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Scimatic Chain (ID: 481)
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