Bisphenol A-Induced Ovotoxicity Involves DNA Damage Induction to Which the Ovary Mounts a Protective Response Indicated by Increased Expression of Proteins Involved in DNA Repair and Xenobiotic Biotransformation

Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous human exposure. BPA causes primordial follicle loss and DNA damage in germ cells, thus we hypothesized that BPA induces ovarian DNA damage, thereby precipitating follicle loss. We also anticipated that the ovary activates DNA repa...

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Bibliographic Details
Published in:Toxicological sciences 2016-07, Vol.152 (1), p.169-180
Main Authors: Ganesan, Shanthi, Keating, Aileen F
Format: Article
Language:English
Subjects:
Activation, Metabolic
Animals
Animals, Newborn
Apoptosis Regulatory Proteins - metabolism
Benzhydryl Compounds - metabolism
Benzhydryl Compounds - toxicity
DNA Breaks, Double-Stranded
DNA Repair
DNA Repair Enzymes - genetics
DNA Repair Enzymes - metabolism
Endocrine Disruptors - metabolism
Endocrine Disruptors - toxicity
Female
Ovarian Follicle - drug effects
Ovarian Follicle - metabolism
Ovarian Follicle - pathology
Ovary - drug effects
Ovary - metabolism
Ovary - pathology
Oxidative Stress - drug effects
Phenols - metabolism
Phenols - toxicity
Phosphatidylinositol 3-Kinase - metabolism
Rats, Inbred F344
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction - drug effects
Time Factors
Tissue Culture Techniques
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Summary:Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous human exposure. BPA causes primordial follicle loss and DNA damage in germ cells, thus we hypothesized that BPA induces ovarian DNA damage, thereby precipitating follicle loss. We also anticipated that the ovary activates DNA repair and xenobiotic biotransformation to minimize oocyte damage and/or, activate cell death signaling to deplete follicles. Postnatal day 4 F344 rat ovaries were cultured in medium containing vehicle control (1% dimethylsulfoxide [DMSO]) ± BPA (440 µM) for 2-8 days. BPA reduced (P < 0.05) small primary, large primary and secondary follicle numbers after 2 days, followed by a reduction (P 
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfw076