Toxicogenomic profiles in relation to maternal immunotoxic exposure and immune functionality in newborns.
A crucial period for the development of the immune system occurs in utero. This results in a high fetal vulnerability to immunotoxic exposure, and indeed, immunotoxic effects have been reported, demonstrating negative effects on immune-related health outcomes and immune functionality. Within the NewGeneris cohort BraMat, a subcohort of the Norwegian Mother and Child Cohort Study (MoBa), immunotoxicity was demonstrated for polychlorinated biphenyls and dioxins, showing associations between estimated maternal intake levels and reduced measles vaccination responses in the offspring at the age of 3. The present study aimed to investigate this link at the transcriptomic level within the same BraMat cohort. To this end, whole-genome gene expression in cord blood was investigated and found to be associated with maternal Food Frequency Questionnaires-derived exposure estimates and with vaccination responses in children at 3 years of age. Because the literature reports gender specificity in the innate, humoral, and cell-mediated responses to viral vaccines, separate analysis for males and females was conducted. Separate gene sets for male and female neonates were identified, comprising genes significantly correlating with both 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and polychlorinated biphenyls (PCB) exposure and with measles vaccination response. Noteworthy, genes correlating negatively with exposure in general show positive correlations with antibody levels and vice versa. For both sexes, these included immune-related genes, suggesting immunosuppressive effects of maternal exposure to TCDD and PCB at the transcriptomic level in neonates in relation to measles vaccination response 3 years later.
Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
Kevin
K
Hochstenbach
D M
DM
van Leeuwen
H
H
Gmuender
R W
RW
Gottschalk
S B
SB
Stølevik
U C
UC
Nygaard
M
M
Løvik
B
B
Granum
E
E
Namork
H M
HM
Meltzer
J C
JC
Kleinjans
J H M
JH
van Delft
Henk
H
van Loveren
D015331:Cohort Studies; D015930:Diet Records; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D008458:Measles Vaccine / Q000276:immunology; D010597:Pharmacogenetics; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011795:Surveys and Questionnaires; D059467:Transcriptome
D000922:Immunotoxins; D008458:Measles Vaccine; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls