Pilot study of gestational PFAS exposure on child blood transcriptional profiles 2259999

Abstract Introduction Per and polyfluoroalkyl substances (PFAS) are persistent fluorinated pollutants that have been shown to impair the immune response. We aimed to ascertain the association of prenatal PFAS exposure with childhood immune system status in those born either inside or outside a community with significant PFAS contamination in drinking water. Methods This pilot study used blood samples collected 10-15 years after birth from 24 mother-child pairs: 12 born inside the community (11 male/1 female) and 12 born outside (5 male/7 female). Blood PFAS levels were measured in samples from both mother and child. Transcriptome sequencing analysis of total RNAs isolated from child blood samples was performed to assess potential prenatal PFAS exposure-related gene expression changes. The differential gene expression analysis focused on 16 males (since there was only 1 non-community born female), and used birth community status as the surrogate for prenatal exposure. Covariates in the model included child BMI, years child spent in the community post-birth, ethnicity, and mom and child blood PFAS levels. Gene Ontology (GO) and Gene Set Enrichment Analyses (GSEA) were used to identify biological functions enriched in differentially expressed genes. Results We identified 842 differentially expressed genes between community-born/non-community born males. The top enriched GO pathways were involved in metabolism, protein breakdown, and cell cycle regulation. GSEA analysis using immune gene sets as reference revealed that the immune genes repressed in community-born males were previously associated with the response to RSV infection in infants. Conclusion Despite the small sample size, we were able to observe significant associations of prenatal PFAS exposure and changes in child blood gene expressions. Ongoing analysis includes cell type deconvolution analysis using RNA-seq data to investigate potential changes in immune cell types between birth communities. Funding Source CHHE ES025128, NIEHS R21ES029353, P42 ES031009, U24 ES037001 Topic Categories Computational and Systems Immunology (COMP)