Yale researchers may have solved a fundamental medical mystery: how bisphenol A (BPA), a ubiquitous plastics component, changes genetic chemistry and impairs fertility.
The Yale team's findings, previewed earlier this month to the Endocrine Society, a 14,000-member scientific and medical professional organization devoted to hormone system research and treatment, have intensified scientists' concern that exposure BPA, a synthetic estrogen that disrupts the endocrine system, may have grave consequences for human reproduction.
In an interview, study co-author Hugh S. Taylor, M.D., professor and chief of the reproductive endocrinology section at Yale University School of Medicine, said his team injected pregnant mice with BPA for just one week. After those mice, and a control group, gave birth, the scientists found that the genetic chemistry of female offspring exposed to BPA in the womb had been irrevocably altered.
A particular gene known as HOXA10, responsible for normal uterine development and fertility in both mice and humans, had been stripped of numerous so-called "methyl groups," each composed of a single hydrogen atom and three carbon atoms.
"We've discovered the exact mechanism by which BPA affects this gene," Taylor said. "This small group can have a powerful effect in turning genes on and off."
BPA scrambles mouse fertility gene's on-off switch
The HOXA10 gene's loss of methyl groups, Taylor and his colleagues determined, caused the uterine lining to become "hyper-responsive" to estrogen - and "out of sync" with the needs of a fertilized egg. A female mouse exposed to BPA in utero could conceive normally but her ability to carry a pregnancy to term might be compromised.
The chemical industry insists that neither the Yale study nor any other amounts to proof positive that BPA causes human infertility or other serious health conditions associated with the chemical in animal experiments.
The Yale scientists don't claim to have settled the many questions about BPA's impact on human health. They administered a higher BPA dosage to the lab mice than the general human exposure level. Their study, a work in progress, has yet to be published in a peer-reviewed scientific journal and corroborated by other researchers. They are planning more research on exactly how much, or little, BPA it takes to jumble a test animal's genetic chemistry.
"Permanent and irreversible" fertility loss
But their findings, which are concrete and specific, have already attracted considerable attention among a growing number of scientists studying BPA's complex interactions with living things.
"It's troubling that the changes are permanent and irreversible," Taylor said of the mouse infertility findings. "I don't want to say that at typical human exposure, there's clear and present danger, but there's enough concern that there might be to warrant further investigation."
BPA linked to heart irregularities
Two other research studies presented at the annual Endocrine Society meeting raised new questions about BPA and health:
•A University of Cincinnati team led by scientist Scott Belcher, Ph.D., linked BPA exposure to arrhythmias-- irregular heartbeats -- in female (but not male) rats and mice.
•Pioneer BPA researcher Frederick Vom Saal, Ph.D., of the University of Missouri-Columbia outlined a new estimate that Americans' exposure to BPA is probably significantly higher than the U.S. government's maximum "safe" dosage.
Hormone experts press for new restrictions on BPA and other chemicals
These and other recent reports caused the Endocrine Society, the world's oldest and largest professional organization devoted to research and clinical practice on hormones and endocrinology, to take the unusual step of issuing its first "scientific statement" declaring that BPA and other endocrine-disrupting chemicals in food, water and consumer products represent a "significant concern to public health." The society vowed to press for new government regulations to "decrease human exposure to the many
endocrine-disrupting agents."
Andrea Gore, Ph.D., a University of Texas pharmacology professor who helped spearhead the society's unprecedented move into public policy, said the weight of evidence is now substantial that chemicals that mimic or disturb hormone activity are corroding public health in many ways, from decreasing fertility to increasing incidence of some cancers. The scientific statement stressed that during critical developmental periods in early life, exposures to even very low levels of endocrine disruptors could have consequences decades later.
Developing children face most severe chemical threat
"If something disrupts the endocrine system of a fetus or infant," said Gore, "you may not know there's a problem until the exposed individual suddenly discovers she's infertile. That may not be until 20 to 40 years later."
Some cancer, she said, may be a delayed reaction to early exposures to environmental chemicals. "We believe the predisposition to certain kinds of cancers such as breast, prostate, uterine, testicular and otherhormonally-sensitive cancers, is set very early in life," she said. "Our likelihood of developing disease depends upon complex interactions between our genes and our environment - and changing the hormonal environment early
in life through exposure to endocrine disruptors can predispose us to an increased risk of developing these diseases in adulthood or with aging."
Hormone experts: Chemicals should be considered dangerous until proven safe
"Although much recent attention has focused on BPA, I don't think we can stop there," said Gore, who is researching the endocrine-disrupting properties of polychlorinated biphenyls (PCBs), industrial chemicals banned in 1977 but still detectable in most people and wildlife. "We need to learn from BPA, PCBs and other endocrine disruptors such as pesticides, fungicides, plastics and plasticizers that we cannot assume that a product
is safe until it is proven otherwise."
Among the Endocrine Society's recommendations: reverse current U.S. policy and treat that chemical compounds as potentially hazardous until shown to be safe. "This is a complete philosophical shift," said Gore, "and one that will require cooperation among individual researchers, clinicians, scientific societies and policy makers."
But as scientists implicate BPA in a lengthening roster of ailments -- among them, cancer, reproductive and cardiovascular system disorders, brain and neurological system dysfunctions, behavioral problems, diabetes and obesity -- they are galvanizing political and regulatory efforts to rein in environmental pollutants whose mysteries are only beginning to be unraveled.