In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis.
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.
Institute of Environmental Medicine,  Karolinska Institutet, 17177 Stockholm,  Sweden.
Sultan
S
Ahmed
Khalid Bin
KB
Ahsan
Maria
M
Kippler
Akhirunnesa
A
Mily
Yukiko
Y
Wagatsuma
A M Waheedul
AM
Hoque
Pa Tamba
PT
Ngom
Shams
S
El Arifeen
Rubhana
R
Raqib
Marie
M
Vahter
D000328:Adult; D017209:Apoptosis; D001151:Arsenic / Q000633:toxicity*; D001459:Bangladesh; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D018384:Oxidative Stress; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D017931:DNA Primers; D001151:Arsenic