RESUMO
BACKGROUND: Cadmium (Cd) and selenium (Se) antagonistically influence redox balance and apoptotic signaling, with Cd potentially promoting and Se inhibiting oxidative stress and apoptosis. Alterations to placental redox and apoptotic functions by maternal exposure to Cd and Se during pregnancy may explain some of the Cd and Se associations with fetal development. OBJECTIVES: Investigate associations between Cd and Se concentrations in maternal toenails with placental expression patterns of tumor necrosis factor (TNF) and steroidogenic genes involved in redox reactions and test associations with fetal growth. METHODS: In a sub-sample from the Rhode Island Child Health Study (n = 173), we investigated the relationships between: (1) maternal toenail Cd and Se concentrations and fetal growth using logistic regression, (2) Cd and Se interactions with factor scores from placental TNF and steroidogenic expression patterns (RNAseq) using linear models, and (3) TNF and steroidogenic expression factors with fetal growth via analysis of covariance. RESULTS: Se was associated with decreased odds of intrauterine growth restriction (IUGR) (OR = 0.27, p-value = 0.045). Cd was associated with increased odds of IUGR (OR = 1.95, p-value = 0.13) and small for gestational age (SGA) births (OR = 1.46, p-value = 0.11), though not statistically significant. Cd and Se concentrations were antagonistically associated with placental TNF and steroidogenic expression patterns, which also differed by birth size. CONCLUSIONS: Se may act as an antagonist to Cd and as a modifiable protective factor in fetal growth restriction, and these data suggest these effects may be due to associated variations in the regulation of genes involved in placental redox balance and/or apoptotic signaling.
Assuntos
Cádmio/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Exposição Materna , Placenta/efeitos dos fármacos , Selênio/toxicidade , Adulto , Feminino , Humanos , Placenta/metabolismo , Gravidez , Rhode IslandRESUMO
BACKGROUND: Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority. OBJECTIVE: We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh. METHODS: The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 x 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up. RESULTS: Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-mug/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00-0.20] and 0.33 ng/mL (95% CI, 0.15-0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-microg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01-0.22) and 0.17 ng/mL (95% CI, 0.00-0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period. CONCLUSIONS: The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.