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 (PCB) found in flame retardant cloth, paint, adhesives and electrical transformers, can interfere with thyroid hormone action in pregnant women and may travel across the placenta to affect the fetus.
In this prospective birth cohort study, researchers looked at the effects of low-dose chemical exposure in 164 pregnant women. Tissue from their placentas, the uterine structure that provides oxygen and nutrients to the fetus, was analyzed for a specific enzyme, CYP1A1, which changes endocrine-disrupting chemicals into a form that can interfere directly with the body’s thyroid hormone receptors.
Abstract
Context
Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH.
Objective
The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta.
Methods
One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR.
Results
CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression.
Conclusions
CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.
Sources and more information
- Endocrine disruptors alter thyroid levels in pregnancy, may affect fetal brain development, eurekalert, 4-Dec-2014.
- Endocrine Disruption in Human Placenta: Expression of the Dioxin-Inducible Enzyme, Cyp1a1, Is Correlated With That of Thyroid Hormone-Regulated Genes, Endocrine Society, October 09, 2014.