BPA raises uterine gene activity in mice exposed before birth.

Bromer, JG, Y Zhou, MB Taylor, L Doherty and HS Taylor. 2010. Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. The FASEB Journal http://dx.doi.org/10.1096/fj.09-140533.

Scientists from Yale University have figured out how bisphenol A (BPA) alters an important gene that guides how the uterus develops in people and rodents. Rather than causing mutations, the chemical affects the gene's on/off markers – what is called an epigenetic change.

Results of the mouse study shows exposure to BPA in the womb removed the "off" tag, allowing the gene – called Hoxa10 – to turn on in the presence of estrogen. BPA-exposed female mice had 25 percent higher activity from the Hoxa10 gene in their reproductive tract than the unexposed mice. The changes remained even after exposure stopped, suggesting they are permanent.

BPA is known to alter genes in an epigenetic way. Some research links this kind of change to the Hoxa10 gene with several cancers and endometriosis in women.

Overall, the results provide more evidence that fetal exposure to BPA changes development of the uterus. The study supports previously published findings that show BPA can affect the Hoxa10 gene. But, this is the first time researchers have shown how the chemical actually affects the gene.

Each year, billions of pounds of BPA are manufactured and used in a variety of products, including polycarbonate plastics, epoxy resins that line food cans, dental sealants and some thermal paper. Because it is used so broadly, almost everyone has BPA in their bodies, and it can pass from mother to fetus. BPA is known to act like an estrogen in people and animals. Therefore, its effects on the reproductive tract are potentially concerning. In studies, BPA can alter reproduction, increase breast and prostate cancer and affect weight gain.

Pregnant mice in this study were treated with a high dose – 5 milligrams per kilogram – of BPA for one week during  pregnancy. High doses in these types of experiments can create dramatic changes so researchers can pinpoint the mechanism of how a chemical may influence genes or cell actions. It is unlikely people would be exposed to such high levels.

The female mice exposed to BPA during development had fewer methyl tags on the Hoxa10 gene in the uterus than the unexposed mice. Hoxa10 controls development of the uterus. Methyl tags prevent genes from being turned on.

Because BPA decreased the number of tags, the Hoxa10 gene was turned on at a time in development when normally it is kept off. The uterine tissue, then, responded differently to normal estrogen signals. Exposures like these that occur during fetal development can sometimes change normal hormone responses in adult animals, leading to health problems such as cancer or altered reproduction.

Even when BPA treatment ended, the methyl tags were still missing from the gene. This suggests that the effects of BPA on the expression of genes can be long lasting or even permanent.