A new study led by biologist R. Thomas Zoeller of the University of Massachusetts Amherst provides the strongest evidence to date that endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) — once widely used in flame retardant cloth, paints, adhesives and electrical transformers — can interfere with thyroid hormone action during pregnancy and may cross the placenta to influence fetal development.
The study’s results were published in an early online edition and in the December print issue of the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism, and the paper was recently recognized as an “extramural paper of the month” by the National Institute of Environmental Health Sciences.
Zoeller explains that PCBs act as endocrine-disrupting chemicals by altering the function of thyroid hormones at the cellular level rather than by changing the total amount of hormone measured in the bloodstream. “PCBs can disrupt how thyroid hormone works without necessarily changing overall hormone concentrations,” he says. “Because many studies only measure circulating hormone levels, they can miss these more subtle but potentially important effects on thyroid-related activity in tissues. Those disruptions may be significant for fetal brain development, even when maternal hormone tests appear normal.”
Although many PCB uses were banned in the United States in 1979, PCBs persist in the environment through releases from disposal sites and from older products still in circulation. As a result, low-level exposure to PCBs remains common in the general population, and pregnant women may carry these residues that can interact with placental tissues.
To investigate how low-dose exposure to endocrine disruptors might affect pregnancies, the research team conducted a prospective birth cohort study with 164 pregnant women. They analyzed placental tissue — the organ that supplies oxygen and nutrients to the developing fetus — for the expression of a specific enzyme, CYP1A1. This enzyme converts certain environmental chemicals into forms that can bind to and interfere with thyroid hormone receptors in cells.
The research combined expertise from the biology department at the University of Massachusetts Amherst with clinical epidemiology from a large cohort assembled by Larissa Takser and colleagues at the University of Sherbrooke, Québec. Biochemistry and experimental work carried out over a decade in Zoeller’s laboratory provided the mechanistic framework that guided the placental analyses. “That prior laboratory work helped us predict specific molecular events that might occur in the placenta,” Zoeller notes. “So far, our observations are consistent with those predictions.”
In their analyses, the investigators observed that placentas with elevated CYP1A1 expression also exhibited changes consistent with altered thyroid signaling. Specifically, two genes normally regulated by thyroid hormones showed higher expression in these placental samples, while circulating maternal thyroid hormone levels remained unchanged. These results suggest that disruptions in thyroid hormone action can be tissue-specific and may not be detectable through standard blood tests alone.
“What we observe in the placenta likely reflects similar processes occurring in the fetus,” Zoeller says. “To fully assess how endocrine-disrupting chemicals affect pregnancy outcomes and fetal development, studies must examine hormone activity at the cellular and molecular levels in target tissues as well as hormone concentrations in blood.”
The study also highlights a potential interaction between environmental chemicals and lifestyle exposures. The enzyme CYP1A1 normally helps metabolize and clear pollutants from the bloodstream, but its expression increases after exposure to cigarette smoke. The research team found that pregnant women who smoked tended to have higher placental levels of CYP1A1, raising the possibility that smoking could amplify placental activation of environmental contaminants that interfere with thyroid signaling.
Authors on the paper include Thomas L. Wadzinski, Katherine Geromini, Judy McKinley Brewer and Ruby Bansal from UMass Amherst, along with Nadia Abdelouahab, Marie-France Langlois and Larissa Takser from the University of Sherbrooke, with R. Thomas Zoeller as the lead investigator. The paper, titled “Endocrine Disruption in Human Placenta: Expression of the Dioxin-Inducible Enzyme, Cyp1a1, Is Correlated With That of Thyroid Hormone-Regulated Genes,” was published online October 9, 2014, in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/jc.2014-2629).
Contact: Janet Lathrop – University of Massachusetts Amherst
Source: University of Massachusetts Amherst press release
Image Source: The photograph is credited to Skitterphoto and is in the public domain
Original Research: Abstract for “Endocrine Disruption in Human Placenta: Expression of the Dioxin-Inducible Enzyme, Cyp1a1, Is Correlated With That of Thyroid Hormone-Regulated Genes” by Thomas L. Wadzinski et al., Journal of Clinical Endocrinology & Metabolism, published online October 9, 2014 (doi:10.1210/jc.2014-2629).