BPA, Common Chemical, Affects Sex in Mice; Warning for Us?

Feb. 15, 2013 — -- In California there's a mouse called, not surprisingly, the California mouse (Peromyscus californicus) that has attracted the attention of scientists because of a reproductive trait that is not always celebrated among humans. The mouse is monogamous, and the male even hangs around to protect the home and help raise the kids.

And now the big-eared critter may just help protect future generations from reproductive disasters. That's true for mice, and quite possibly for humans.

New evidence suggests that exposure to a chemical that is now carried in nearly all of us can alter the reproductive system for many generations to come. The chemical, known as bisphenol A (BPA), has been the subject of environmental debate for years. It is present in food and beverage containers ranging from soup to beer, and it is common for it to leach into the contents and thus become part of our diet.

The Centers for Disease Control and Prevention found detectable levels of the chemical in 93 per cent of 2,517 urine samples from people six years and older.

"It's everywhere," Cheryl Rosenfeld, associate professor of biomedical sciences at the University of Missouri, said in a telephone interview. "It does not break down in the environment. Almost every water source that has been tested to date has been found to contain detectable levels, so this is a global concern."

BPA has mostly been used in hard plastics and as a sealant in metal containers. But it became highly controversial in 2008 when several studies suggested it might be toxic, especially to young children. There has been much controversy ever since over whether the chemical is harmful, and government agencies have sent mixed messages.

Canada, for example, bans it in baby bottles, but has twice concluded it does not "pose a health risk to the general population, including newborns and young children." The U.S. Food and Drug Administration has banned it in all baby products, but has consistently declared that the evidence is not sufficient to merit further measures, at least for now. However, the FDA says on its website that recent research has left the agency with "some concerns" about BPA's safety.

Rosenfeld has taken a somewhat different approach than other researchers. Her evidence indicates that an expectant mother who has been exposed to BPA may jeopardize reproduction in many subsequent generations. And chances are that mom's getting BPA without even knowing it.

Boys and girls are different, as we all know, and that basic fact became the focus of several research papers by Rosenfeld and her colleagues. She wanted to know if BPA could affect prenatal development in a mother's womb, because the chemical mimics the role of important sex hormones, specifically testosterone and estrogen.

"It will bind to the same receptors that the natural hormone would bind to," she said. "But it's not regulated in a tight fashion like the natural hormones would be. So it kind of indiscriminately acts, and there's no ability to regulate it."

It becomes a rogue hormone during the most critical phase in an organism's life, the development period prior to birth.

She initially studied deer mice, which are not monogamous. In a startling study released in 2011, she found that male offspring from a female mouse who was exposed to BPA during pregnancy were "demasculinized," and behaved more like females, suggesting that the chemical had damaged behavioral and cognitive traits that are unique to each sex and important in reproduction.

But she wanted to do a similar study involving mice that are more like humans in their social and reproductive lives. So she turned to the California mouse, and found that exposure to BPA resulted in male offspring that neglected to mark their territory. That's an essential function in protecting the home and foraging for resources. In short, the males lost interest in the family.

"Even if you don't affect the reproductive system per se, just by affecting the behaviors that are essential for animals to reproduce has long term consequences," she said. "Those animals exposed to BPA will have decreased likelihood of finding a mate and reproducing. And if they do reproduce, our studies suggest they will essentially be passing on those compromised traits to future generations.

"So the long term will see a decrease in the reproductive fitness of the subsequent generations."

That finding, published in the journal PLOS One, along with research at several other labs, has pushed concerns higher, but so far little has been done to deal with the issue.

"There hasn't been one legislation passed to date to control the most alarming way we are being exposed to BPA, and that's through the pregnant mother" Rosenfeld said.

One of the most troubling findings in her latest study is that prenatal exposure to the chemical caused reproductive changes in the offspring that did not go away with the passage of time. The changes got stronger, not weaker.

Her research adds substantially to a growing body of literature showing there is need for real concern, and prompt action, but the data so far is not likely to convince everyone. What's true for the California mouse does not necessarily apply to humans -- because there is obviously a wide gap between humans and mice -- and it would not be ethically possible to replicate Rosenfeld's experiments with human subjects.

Two years ago, the American Medical Association called for legislation to force companies to label products that have BPA in them.

"That should be mandatory, but it's not required at this time," Rosenfeld said. However, some manufacturers have voluntarily pulled it from their products.

The widening use of plastics in all types of containers is likely to worsen the situation. Currently, "we produce about eight to 10 billion pounds per year, and that number is going to go up astronomically," Rosenfeld said.