期刊
TOXICOLOGICAL SCIENCES
卷 129, 期 2, 页码 305-314出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfs202
关键词
sjTREC; thymus; oxidative stress; apoptosis; arsenic; cord blood
类别
资金
- Swedish International Development Cooperation Agency (Sida) [75000431, 75000512, 82030018]
- European Commission (PHIME project) [FOOD-CT-2006-016253]
- University of Tsukuba (JSPS) [18256005]
- Karolinska Institutet
- International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)'s core donors
- ICDDR,B
- UNICEF
- Sida
- U.K. Medical Research Council
- Swedish Research Council
- DFID, Japan Society for the Promotion of Science (JSPS)
- Child Health and Nutrition Research Initiative (CHNRI)
- Uppsala University
- U.S. Agency for International Development (USAID)
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, In U-As (GW8) was inversely associated with In sjTRECs in CBMC (B = -0.25; 95% confidence interval [CI] -0.48 to -0.01). Using multivariable-adjusted spline regression, In U-As (GW30) and In B-As (GW14) were inversely associated with In 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 mu g/l and B-As 6 mu g/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 CI8(+). 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.
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