Toxicogenomic Profiles in Relation to Maternal Immunotoxic Exposure and Immune Functionality in Newborns

Abstract

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.

Linking the Aryl Hydrocarbon Receptor with Altered DNA Methylation Patterns and Developmentally Induced Aberrant Antiviral CD8+ T Cell Responses

“…These observations suggest early life AHR activation influences CD8 + T cell function later in life without causing overt immunotoxicity. Consistent with these potential mechanisms discussed here, recent human transcriptomic data show correlations between fetal exposure to AHR-binding pollutants, including TCDD, and altered expression of genes involved in immune regulation, cell cycle and antigen processing and presentation in cord blood cells (62). …”

Making sense of OMICS data in population‐based environmental health studies

“…The gender‐specific effects observed in this study were confirmed and extended in a second study on cord blood samples from 45 male and 66 female newborns [Hochstenbach et al, ] which made use of transcriptomics as well as multiple additional biomarkers. These biomarkers included (a) DR‐, ER‐ and AR‐CALUX, which reflect exposure to chemicals interacting with the dioxin‐, estrogen‐, and androgen‐receptors, respectively (e.g., polychlorinated dibenzodioxins, dibenzofurans and biphenyls, and endocrine disruptors such as DDT and antiandrogens), (b) haemoglobin adducts of acrylamide and glycidamide, biomarkers of dietary exposure to acrylamide produced during food processing, and (c) micronuclei as a biomarker of cancer risk.…”

Immunotoxicology: A brief history, current status and strategies for future immunotoxicity assessment

“…For example, Hochstenbach et al [37] established toxicogenomic profiles in relation to maternal immunotoxic exposure and immune functionality in newborns, and Pennings et al [38] found cord blood gene expression profiles supporting that prenatal exposure to perfluoralkyl substances caused depressed immune functionality in early childhood. In vitro assays which evaluate immunosuppression are generally not used to form a basis for risk assessment.…”