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. 2011 Feb;119(2):258-64.
doi: 10.1289/ehp.1002086. Epub 2010 Oct 12.

Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood

Sultan Ahmed  1 , Sultana Mahabbat-e Khoda, Rokeya Sultana Rekha, Renee M Gardner, Syeda Shegufta Ameer, Sophie Moore, Eva-Charlotte Ekström, Marie Vahter, Rubhana Raqib
Affiliations

Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood

Sultan Ahmed et al. Environ Health Perspect. 2011 Feb.

Abstract

Background: Arsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight.

Objectives: In 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.

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 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.

Results: In 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.

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.

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Figures

Figure 1
Figure 1
(A and B) Association between U-As and frequencies of placental CD3+ and CD8+ cells, using quartiles of U-As concentrations at GW8 (A; n = 130, 32–33 in each quartile; median U-As, 26, 46, 115, and 341 μg/L, respectively) and GW30 (B; n = 130, 32–33 in each quartile; median U-As, 27, 48, 121, and 335 μg/L, respectively). (C and D) Association between U-As and expression of CD64+ and CD68+ cells, using quartiles of U-As exposure at GW8 (C) and GW30 (D). (E and F) Association between U-As and 8-oxoG and leptin expression, using quartiles of U-As exposure at GW8 (E) and GW30 (F). (G and H) Association between U-As and TNFα, IFNγ, and IL-1β expression, using quartiles of U-As concentrations at GW8 (G) and GW30 (H). Data are means ± SE. Ln, natural log. *p < 0.05 for U-As modeled as a continuous variable in multivariable-adjusted linear regression analysis (Table 2).
Figure 2
Figure 2
Association of As exposure at GW30 with cord blood cytokines (TNFα, IL-1β, IL-8, and IFNγ). Concentrations of cord blood cytokines in different quartiles of U-As concentrations at GW30 (as in Figure 1H) are expressed as mean ± SE. Ln, natural log.
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