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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
In Utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis
Toxicological Sciences, Volume 129, No. 2, Year 2012
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Description
Prenatal arsenic exposure is associated with increased infant morbidity and reduced thymus size, indicating arsenic-related developmental immunotoxicity. We aimed to evaluate effects of prenatal arsenic exposure on thymic function at birth and related mechanisms of action. In a Bangladeshi cohort, arsenic was measured in urine (U-As, gestational week (GW) 8 and 30) and blood (B-As, GW14) in 130 women. Child thymic index was measured by sonography at birth and thymic function by signal-joint T-cell receptor-rearrangement excision circles (sjTRECs) in cord blood mononuclear cells (CBMC). In a subsample (n = 44), sjTRECs content in isolated CD4+ and CD8+ T cells, expression of oxidative-stress defense and apoptosis-related genes in CBMC, arsenic concentrations (urine, placenta, and cord blood), and oxidative stress markers in placenta and cord blood were measured. In multivariable-adjusted regression, ln U-As (GW8) was inversely associated with ln sjTRECs in CBMC (B = -0.25; 95% confidence interval [CI] -0.48 to -0.01). Using multivariable-adjusted spline regression, ln U-As (GW30) and ln B-As (GW14) were inversely associated with ln sjTRECs in CBMC (B = -0.53; 95% CI -0.93 to -0.13 and B = -1.27; 95% CI -1.89 to -0.66, respectively) below spline knots at U-As 150 μg/l and B-As 6 μg/kg. Similar inverse associations were observed in separated CD4+ and CD8+ T cells. Arsenic was positively associated with 8-hydroxy-2'-deoxyguanosine in cord blood (B = 0.097; 95% CI 0.05 to 0.13), which was inversely associated with sjTRECs in CD4+ and CD8+ T cells. In conclusion, prenatal arsenic exposure was associated with reduced thymic function, possibly via induction of oxidative stress and apoptosis, suggesting subsequent immunosuppression in childhood. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Authors & Co-Authors
Ahmed, Sultan M.
Sweden, Stockholm
Karolinska Institutet
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Ahsan, Khalid Bin
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Kippler, Maria J.
Sweden, Stockholm
Karolinska Institutet
Mily, Akhirunnesa
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Wagatsuma, Yukiko
Japan, Tsukuba
University of Tsukuba
Waheedul Hoque, A. M.
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Ngom, Pa Tamba
Gambia, Banjul
Medical Research Council Laboratories Gambia
Arifeen, Shams E.
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Raqib, Rubhana
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Vahter, Marie E.
Sweden, Stockholm
Karolinska Institutet
Statistics
Citations: 109
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1093/toxsci/kfs202
e-ISSN:
10960929
Research Areas
Cancer
Maternal And Child Health
Study Design
Cohort Study
Participants Gender
Female