Arsenic-Associated Oxidative stress, Inflammation, and Immune Disruption in Human Placenta and Cord Blood

• BACKGROUND: Arsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight. OBJECTIVES: This study aimed to elucidate the effects of As exposure on immune markers in the placenta and cord blood, and the involvement of oxidative stress. METHODS: Pregnant women were enrolled around gestational week (GW) 8 in our longitudinal, population-based, mother-child cohort in Matlab, an area in rural Bangladesh with large variations in As concentrations in well water. Women (n=130) delivering at local clinics were included in the present study. We collected maternal urine twice during pregnancy (GW8 and 30) for measurements of As, and placenta and cord blood at delivery for assessment of immune and inflammatory markers. Placental markers were measured by immunohistochemistry and cord blood cytokines by multiplex cytokine assay. RESULTS: In multivariable adjusted models, maternal urinary As (U-As) exposure both at GW8 and 30 was significantly positively associated with placental markers of 8-oxoguanine (8-oxoG) and IL-1β, U-As at GW8 with TNF- α and IFN-γ, U-As at GW30 with leptin , and U-As at GW8 was inversely associated with CD3-T cells in the placenta. Cord blood cytokines (IL-1β, IL-8, IFN-γ, TNF-α) showed a U-shaped association with U-As at GW30. Placental 8-oxoG was significantly positively associated with placental pro-inflammatory cytokines. Multivariable adjusted analyses suggested that enhanced placental cytokine expression (TNF-α and IFN-γ) was primarily influenced by oxidative stress, while leptin expression appeared to be mostly mediated by As, and IL-1β appeared to be influenced by both oxidative stress and As. CONCLUSION: As exposure during pregnancy appeared to enhance placental inflammatory responses (in part by increasing oxidative stress), reduce placental T cells, and alter cord blood cytokines. These findings suggest that effects of As on immune function may contribute to impaired fetal and infant health.

Nyckelord

arsenic

cytokines

8-oxoguanine

leptin

oxidative stress

placenta

MEDICINE

MEDICIN

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