Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities.
Bisphenol A (BPA) is a highly prevalent constituent of plastics that has been associated with diabetes, cardiovascular disease, and an increased risk of miscarriages in humans. In mice, BPA exposure disrupts the process of meiosis; however, analysis of the affected molecular pathways is lagging and has been particularly challenging. Here we show that exposure of the nematode Caenorhabditis elegans to BPA, at internal concentrations consistent with mammalian models, causes increased sterility and embryonic lethality. BPA exposure results in impaired chromosome synapsis and disruption of meiotic double-strand break repair (DSBR) progression. BPA carries an anti-estrogenic activity in the germline and results in germline-specific down-regulation of DSBR genes, thereby impairing maintenance of genomic integrity during meiosis. C. elegans therefore constitutes a model of remarkable relevance to mammals with which to assess how our chemical landscape affects germ cells and meiosis.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Patrick
P
Allard
Monica P
MP
Colaiácovo
D000818:Animals; D001559:Benzhydryl Compounds; D017173:Caenorhabditis elegans; D002853:Chromatography, Liquid; D002869:Chromosome Aberrations / Q000187:drug effects*; D020090:Chromosome Segregation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D018095:Germ-Line Mutation / Q000187:drug effects*; D007211:Indoles; D023421:Models, Animal; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D007211:Indoles; D010636:Phenols; C007293:DAPI; C006780:bisphenol A; D000098826:Bisphenol A Compounds