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Polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury are global environmental contaminants that can disrupt the endocrine system in animals and humans. However, there is little evidence that they can interfere with endocrine status in pregnant women and neonates at low levels of exposure. The aim of this study was to examine thyroid hormone levels during pregnancy and in cord blood in relation to blood concentrations of organochlorine compounds (OCs) and Hg in healthy women recruited during pregnancy. We found a significant negative correlation between maternal total triiodothyronine levels and three non-coplanar congeners (PCB-138, PCB-153, and PCB-180), three pesticides (p,p -DDE, cis-nanochlor, and hexachlorobenzene), and inorganic Hg independently, without any other changes in thyroid status. No significant relationships were observed between OCs and cord serum thyroid hormones. Cord serum free thyroxin was negatively correlated with inorganic Hg. These results suggest that at even low levels of exposure, persistent environmental contaminants can interfere with thyroid status during pregnancy.

Background Polybrominated diphenyl ethers are a group of flame-retardant chemicals appearing increasingly in the environment. Their health effects and mechanisms of toxicity are poorly understood. Objectives We screened for the sensitive effects and mechanisms of toxicity of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses comparable to human exposure. Methods Wistar dams were exposed to vehicle or BDE-47 (0.002 and 0.2 mg/kg body weight) every fifth day from gestation day 15 to postnatal day 20 by injections to caudal vein. Total RNA was extracted from the livers of pups and hybridized to the whole-genome RNA expression microarrays. The list of genes 2-fold differentially expressed was exported to PANTHER and Ingenuity Systems for analysis of enriched ontology groups and molecular pathways. Results Oxidoreductase and transferase protein families were enriched in exposed rats as were these biological process categories: carbohydrate metabolism; electron transport; and lipid, fatty acid, and steroid metabolism. Four signaling pathways (cascades of activation of drug-metabolizing enzymes) and 10 metabolic pathways were significantly enriched. Drug-metabolizing enzymes appear to be regulated by BDE-47 through an aryl hydrocarbon receptor–independent mechanism. Direct interaction with retinoid X receptor or its upstream cascade may be involved. The main metabolic effects consisted of activation of metabolic pathways: α- and ω-oxidation of fatty acids, glycolysis, and starch hydrolysis. Conclusions Altered expression of genes involved in metabolic and signaling pathways and functions of the organism occurs after perinatal exposure of rat offspring to BDE-47 at doses relevant for the general population.

The neurotoxic effects of prenatal exposure to high doses of methylmercury (MeHg) were well established after the serious poisoning epidemics in Japan and Iraq (Harada 1995; Marsh et al. 1987). However, associations between MeHg exposure, developmental milestones, and neurologic tests at exposure levels as low as 10 ppm (estimated in maternal hair) have proven difficult to confirm (Myers and Davidson 2000). Nevertheless, children exposed to mercury levels < 10 ppm have been observed to display subtle neurobehavioral deficits, especially with respect to language, attention, and memory scores (Grandjean et al. 1997; Weihe et al. 2002). In one of three main cohorts, beneficial associations observed between Hg exposure and psychomotor performances (Myers et al. 1995) are believed to be attributable to other nutriments found in fish, such as selenium and/or polyunsaturated fatty acids. Although high-dose MeHg poisoning has been shown to cause developmental disorders, evidence that more subtle low-level developmental exposure contributes to these disorders is limited. Sensitive biomarkers are needed to assess the effects consequent to low-dose exposures. Calcium homeostasis is a known target of several environmental neurotoxicants including lead and Hg (Habermann et al. 1983; Kirk et al. 2003; Marty and Atchison 1997). Deregulation of Ca homeostasis triggers serious effects on cell functioning because of altered Ca signaling. Normally, cytosolic concentration of free Ca2+ (divalent calcium cation) is maintained at low levels (10−7 M) by extrusion and compartmentalization systems. A main component of the extrusion process is the plasma membrane Ca–ATPase pump (Carafoli and Brini 2000). Whereas transient elevations of cytosolic Ca2+ levels are an important component of cell signaling, sustained Ca2+ increases are not tolerated by cells and generally lead to apoptosis or cytotoxicity and necrosis (Orrenius et al. 1989). Intracellular Ca is a sensitive biomarker of pollutant-related stress in amoebic cells exposed to Hg at sub-lethal doses (Dondero et al. 2006). Heavy metals are able to inhibit in vitro Ca pump activity in purified plasma membranes obtained from mussel-gill cells. Experimental studies have shown that Hg2+ inhibits Ca pump activity by preventing the formation of an essential phosphorylated intermediate of the process of Ca2+ transport (Viarengo et al. 1993). One in vitro study reported the compensatory activation of Ca pump protein expression after Hg induced transitory inhibition of Ca pump activity, leading to a net increase in enzyme activity (Burlando et al. 2004). We previously reported a negative association between low prenatal Pb exposure and red-blood-cell Ca pump activity in healthy newborns (Campagna et al. 2000). Because prenatal Hg exposure at high levels induces widespread damage to the developing brain, we assumed that more subtle low-level exposures should trigger more subtle functional disturbances. Accordingly, we hypothesized that Ca pump activity would also be correlated with low-level prenatal Hg exposure. Thus, our objective was to determine the relationships between Hg and Pb prenatal exposures and erythrocyte Ca pump activity in human term newborns and their mothers at delivery. We used Hg content in maternal hair as a biomarker of Hg exposure, which was shown to be highly predictive for MeHg in maternal and cord blood in low-fish-eating pregnant populations (Morrissette et al. 2004).