R. Thomas Zoeller, Ph.D.
University of Massachusetts, Amherst
NIEHS Grant R01ES010026
An NIEHS grantee and colleagues report strong evidence that endocrine-disrupting chemicals can interfere with thyroid hormone action in pregnant women without changing their blood levels of thyroid hormone. The findings show that truly understanding how endocrine-disrupting chemicals may affect pregnancies will require studying not only hormone levels detected in the blood but also hormone activity at the cellular level.
The researchers chose to analyze placental tissue because it is an important regulator of maternal thyroid hormone for the developing fetus. Using placental tissue samples from 164 pregnant women with no thyroid disease, they analyzed the messenger RNA (mRNA) expression for the enzyme CYP1A1. Prior studies showed that CYP1A1 can change certain endocrine-disrupting chemicals, such as PCBs, into a form that can directly activate the body's thyroid hormone receptors.
The researchers found that levels of CYP1A1 mRNA varied 5-fold across the 132 placental samples in which it was detected. Although the mothers’ thyroid hormone blood levels remained the same, pregnancies where the placenta contained higher levels of CYP1A1 mRNA expression tended to exhibit signs of thyroid disruption in the placenta. CYP1A1 mRNA expression also strongly correlated with expression levels of two thyroid-regulated genes. Expression levels of each gene correlated with each other, which suggests that they share a common activator.
The findings are consistent with the hypothesis that CYP1A1 allows some endocrine disrupting chemicals such as PCBs to activate the thyroid hormone receptor. The current study is the first to show this correlation in humans and suggests that CYP1A1 may be an important tissue biomarker of susceptibility to thyroid signaling disruption.
Citation: Wadzinski TL, Geromini K, McKinley Brewer J, Bansal R, Abdelouahab N, Langlois MF, Takser L, Zoeller RT. 2014. Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, Cyp1a1, is correlated with that of thyroid hormone-regulated genes. J Clin Endocrinol Metab; http://dx.doi.org/10.1210/jc.2014-2629