Thoroughly modern maladies

Manmade chemicals have become nearly ubiquitous. Used as solvents, medicines, pesticides, flame retardants, container materials and much more, they are found in the food we eat, the water we drink and the air we breathe. But are they safe?

It’s a big, complicated question with implications for human health, the environment and the economy. And it’s a question that many CALS life scientists are addressing. One of them is Dr. Heather Patisaul, an assistant professor of biology whose studies focus on finding out more about how hormones in early fetal and neonatal development create differences in male and female brain circuits and behaviors.

Patisaul is particularly interested in whether exposure to modern synthetic estrogens alters those sex differences – and if so, how and when these changes take place.

Her research has found that one chemical – Bisphenol A, or BPA – could be cause for concern. Worldwide, millions of tons of BPA are produced each year to make a range of products – from water bottles to eyeglasses to linings for food and beverage cans.

Traces of BPA can be found in the blood and urine of nearly every person in the United States, Patisaul says, and there’s intense debate over whether the rise in its use is responsible for a number of disturbing trends related to human reproduction.

Through research conducted in rats, Patisaul has found that females exposed to low doses in the first four days of life experienced early onset of puberty. The rats went on to develop cyst-like growths in their ovaries, became obese and prematurely lost their estrous cycle – equivalent to a woman’s menstrual cycle.

In male rats exposed to BPA, Patisaul has seen behavioral changes: They are more anxious and less likely to take such risks as spending time in a well-lit maze (rats prefer the dark) or walking along planks that don’t have sides.

Now Patisaul is attempting to find out precisely what happens in the body that leads to those behavioral and physical changes.

“We suspect that endocrine disruptors like BPA are contributing to adverse health outcomes in humans, but we have to pin down the mechanisms if we are really going to make a good case,” she says. “We want to find out what the origins of all those different outcomes are and to try to understand what got perturbed in development that leads to these outcomes.

“After all, a rat is not a little girl,” she says. “But we know that the age of onset of puberty in girls in the United States is dropping. … It can be as young as the first or second grade. So we have to understand if what’s driving early puberty in the rat is potentially something that could be driving puberty in a little girl.”

Because the major changes she has seen with Bisphenol A are related to reproduction and energy balance, Patisaul is eyeing a group of proteins, the RFamide peptides, which regulate gonadotropin secretion and are associated with reproduction and energy balance.

“We think maybe the development of this neural system could be altered by early exposure to BPA,” she says, “so that’s what we are looking at right now.”

Meanwhile, Patisaul is in the beginning stages of a grant-funded project with the U.S. Food and Drug Administration. With the goal of building a BPA risk assessment for humans, the FDA has been collecting data on the growth and development of rats exposed to BPA from birth until adulthood.

Previously, using samples of rat brains from the FDA study, Patisaul and her colleagues used radioactive tags to characterize differences in estrogen receptors in the developing brains of male and female rats. Next, they will be expanding that study to see what happens if they study more animals and use different levels of BPA.

“This study has real implications for human health, because the data will be used by FDA and other regulatory agencies to make decisions about how these chemicals can be used,” Patisaul says.

Dr. Sherry Ferguson, of the FDA’s National Center for Toxicological Research, praised Patisaul’s research, noting that “she has the insight, motivation and enthusiasm to provide important data in this area.”

“The impact of her work is already beginning,” Ferguson says. “Her basic science work has led others to examine the adverse effects of other chemicals on (reproductive) systems.”

While Patisaul continues her BPA research, she is also looking at other chemicals, including flame retardants. Through such studies, she hopes to enrich our understanding of how the reproductive system develops and how exposure to chemicals very early in life affects that development.

That’s important, she says, because there’s growing evidence that what happens very early in life – even in the womb – can set the stage for adult diseases and fertility.

Patisaul also hopes to contribute to the kind of understanding that regulatory agencies need to set informed public policy and that consumers can use to make wise choices about the products they buy and how they use them.

She talks frequently to the news media – she was in TIME magazine in the fall — to raise awareness about endocrine-disrupting chemicals, and she teaches a course on the fetal bases of adult diseases.

“These students are going to become tomorrow’s physicians and chemists and business people. Their generation is going to have to be more thoughtful about this and work to solve these problems, and they need sound science to do that,” she says.

“It’s absolutely definitive now that we have a soup of chemicals in our bodies. They are in our fat, our blood, our urine, our breast milk. They are everywhere. We need to get a grasp on what they might be doing once they get inside of us,” Patisaul concludes. “It’s really important to know if these chemicals are harmful – or innocuous. If they are innocuous, we need to quit worrying about them. And if they are harmful, we need to make decisions about what we are going to do about that.”