Bisphenol A exposure linked to life-long fertility defects, gene changes
The study is the first to show that exposure to the chemical, commonly found in the epoxy linings of food cans and in polycarbonate baby bottles, may permanently affect sensitivity to oestrogen, said the team led by Professor Hugh S Taylor.
DNA alteration
The research project exposed a group of mice to BPA during foetal development and examined both gene expression and the amount of DNA modification in the uterus. A second set of mice was exposed to a placebo.
Scientists found that mice exposed to BPA as a foetus demonstrated an “exaggerated response to oestrogen as adults, long after exposure to BPA”. Contact with the substance permanently reprogrammed the genes to respond excessively to oestrogen.
“The DNA in the uterus was modified by loss of methyl groups so that it responded abnormally in adulthood,” said Taylor. “The gene expression was permanently epigenetically altered and the uterus became hyper-responsive to estrogens.”
Methodology and results
Pregnant CD-1 mice were treated with 5 mg/kg IP doses of either BPA or the control substance on days 9–16 of their pregnancy.
The study evaluated the change on the homeobox gene Hoxa10 – which controls uterine organogenesis – and found its expression was affected by in utero BPA exposure.
“Hoxa10 mRNA and protein expression were increased by 25 per cent in the reproductive tract of mice exposed in utero,” said the research. “Bisulfite sequencing revealed that cytosine-guanine dinucleotide methylation was decreased from 67 to 14 per cent in the promoter and from 71 to 3 per cent in the intron of Hoxa10 after in utero BPA exposure.”
The study also said that exposure to BPA as a foetus is carried throughout adulthood and called for improvements in how these effects are measured during people’s entire lives.
“What our mothers were exposed to in pregnancy may influence the rest of our lives,” said Taylor. “We need to better identify the effect of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors.”
Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response byJason G. Bromer, Yuping Zhou, Melissa B. Taylor, Leo Doherty, and Hugh S. Taylor
Citation: The FASEB Journal (Journal of the Federation of American Societies for Experimental Biology) Vol. 24, Issue 3 (March 2010)
