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PCBs (polychlorinated biphenyls) can interfere with thyroid hormone in
pregnant women and may travel across the placenta to affect the fetus.
PCBs may affect fetal brain
A new study provides the strongest evidence to date that endocrine disrupting chemicals such as PCBs (polychlorinated biphenyls) can interfere with thyroid hormone in pregnant women and may travel across the placenta to affect the fetus.
Polychlorinated biphenyls (PCBs) found in flame retardant cloth, paint, adhesives and electrical transformers, have been found to disrupt the human endocrine system. These chemicals can interfere with the hormones produced by the thyroid gland, and in pregnant women may travel across the placenta to affect the fetus. The study was led by biologist R. Thomas Zoeller, University of Massachusetts at Amherst.
Study results appear in the December print edition of the Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM). The paper was also honored this week as an "extramural paper of the month" by the National Institute of Environmental Health Sciences.
"As endocrine-disrupting chemicals, PCBs interfere with the way the thyroid hormone functions, but they don't actually change the amount of the hormone found in the body. Although these effects are largely invisible in scientific studies that only judge thyroid activity by measuring hormone levels, they may be having a real impact on infant brain development."
R. Thomas Zoeller PhD, University of Massachusetts, Amherst
Although endocrine-disrupting PCBs were banned in the United States in 1979, they are still released into the environment from disposal sites and from products manufactured before the ban. Most people have been exposed to low levels of PCBs, Zoeller adds.
In this prospective birth cohort study, Zoeller and colleagues 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.
Zoeller and colleagues found that in pregnancies where the placenta contained higher levels of CYP1A1, it also showed signs of thyroid disruption. Levels of two thyroid-regulated genes tended to be higher in these pregnancies, although the mother's overall thyroid hormone levels did not change.
Zoeller: "Whatever is happening in the placenta likely reflects what is happening in the fetus. To truly understand how endocrine-disrupting chemicals may be affecting pregnancies, the findings show we need to study not only hormone levels, but hormone activity at the cell level."
The effects of endocrine-disrupting chemicals may be particularly insidious in people who smoke.
The enzyme CYP1A1, which is supposed to clean the blood, is produced in more volume when exposed to cigarette smoke.
Researchers found pregnant women who smoked tended to have higher levels of the CYP1A1 enzyme in their placental tissue.
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.
The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta.
One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Qéubec, 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.
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.
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.
In addition to Zoeller, other authors at UMass Amherst are Thomas Luke Wadzinski, Katherine Geromini, Judy McKinley Brewer and Ruby Bansal, with Nadia Abdelouahab and Marie-France Langlois in addition to Takser at the University of Sherbrooke.
This work was a collaboration between scientists in the biology department at UMass Amherst and physician scientists led by Larissa Takser at the University of Sherbrooke, Québec, who collected placental tissue from a large epidemiological study. Biochemistry and experimental work conducted at Zoeller's UMass Amherst laboratory over the past decade provided the framework for the analyses.
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