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

Abstract

BackgroundArsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight.ObjectivesIn this study we aimed to elucidate the effects of As exposure on immune markers in the placenta and cord blood, and the involvement of oxidative stress.MethodsPregnant 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 GW30) 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.ResultsIn multivariable adjusted models, maternal urinary As (U-As) exposure both at GW8 and at GW30 was significantly positively associated with placental markers of 8-oxoguanine (8-oxoG) and interleukin-1β (IL-1β); U-As at GW8, with tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); and U-As at GW30, with leptin; U-As at GW8 was inversely associated with CD3+ T cells in the placenta. Cord blood cytokines (IL-1β, IL-8, IFNγ, TNFα) showed a U-shaped association with U-As at GW30. Placental 8-oxoG was significantly positively associated with placental proinflammatory cytokines. Multivariable adjusted analyses suggested that enhanced placental cytokine expression (TNFα and IFNγ) was primarily influenced by oxidative stress, whereas leptin expression appeared to be mostly mediated by As, and IL-1β appeared to be influenced by both oxidative stress and As.ConclusionAs 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.

Maternal arsenic exposure and birth outcomes: A comprehensive review of the epidemiologic literature focused on drinking water

“…A recent study reports detectable levels in newborn meconium (Vall et al, 2012). Experimental and observational evidence suggests that iAs accumulates in and disrupts placental function (Ahmed et al, 2011) and alters cord blood methylation (Pilsner et al, 2012). …”

Assessing human metal accumulations in an urban superfund site

“…According to the International Agency for Research on Cancer (IARC, 1980) inorganic arsenic is classified as a human carcinogen, causing skin, lung and bladder cancer. Arsenic is also associated with many non-cancerous outcomes like cardiovascular dysfunction (Chen, Y. et al, 2011; Medrano et al, 2010; Sohel et al, 2009), adverse pregnancy outcomes (Ahmed et al, 2011), cognitive deficits (Wasserman et al, 2007), and type-2 diabetes (Navas-Acien et al, 2008). A limitation to the findings in this study is the lack of speciation of arsenic found at elevated levels in the Butte population.…”

Arsenic exposure causes epigenetic dysregulation of IL-8 expression leading to proneoplastic changes in kidney cells

“…In-utero arsenic exposure could cause immune suppression, impaired thymic development and enhanced morbidity (Raqib et al, 2009). It has also been reported that arsenic exposure during pregnancy potentiates placental inflammatory responses, reduces the number of placental T cells and alters the expression of cord blood cytokines such as IL-1b, IL-8, IFN-g and TNF-a (Ahmed et al, 2011). Prenatal arsenic exposure can also increase proinflammatory response in newborns (Ahmed et al, 2011;Fry et al, 2007).…”