Identification of environmental chemicals targeting miscarriage genes and pathways using the comparative toxicogenomics database.

Environmental Research
Sean M HarrisKelly M Bakulski

Abstract

Miscarriage is a prevalent public health issue and many events occur before women are aware of their pregnancy, complicating research design. Thus, risk factors for miscarriage are critically understudied. Our goal was to identify environmental chemicals with a high number of interactions with miscarriage genes, based on known toxicogenomic responses. We used miscarriage (MeSH: D000022) and chemical gene lists from the Comparative Toxicogenomics Database in human, mouse, and rat. We assessed enrichment for gene ontology biological processes among the miscarriage genes. We prioritized chemicals (n = 25) found at Superfund sites or in the blood or urine pregnant women. For chemical-disease gene sets of sufficient size (n = 13 chemicals, n = 20 comparisons), chi-squared enrichment tests and proportional reporting ratios (PRR) were calculated. We cross-validated enrichment results. Miscarriage was annotated with 121 genes and overrepresented in inflammatory response (q = 0.001), collagen metabolic process (q = 1 × 10-13), cell death (q = 0.02), and vasculature development (q = 0.005) pathways. The number of unique genes annotated to a chemical ranged from 2 (bromacil) to 5607 (atrazine). In humans, all chemicals tested were highly ...Continue Reading

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Citations

Jun 2, 2021·Environmental Science and Pollution Research International·Amalia CecchiMaría Gabriela Rovedatti
Jun 8, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Katarina BaralićDanijela Đukić-Ćosić

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