Length of PM2.5 exposure and alterations in the serum metabolome among women undergoing infertility treatment

Background: Both acute and chronic exposure to fine particulate matter (PM2.5) have been linked to negative health outcomes. Studies have used metabolomics to describe the biological pathways linking PM2.5 with disease but have focused on a single exposure window. We compared alterations in the serum metabolome following various short- and long-term PM2.5 exposures. Methods: Participants were women undergoing in vitro fertilization at a New England fertility clinic (n = 200). Women provided their residential address and provided a blood sample during controlled ovarian stimulation. PM2.5 exposure was estimated in the 1, 2, and 3 days, 2 weeks, and 3 months prior to blood collection using a validated spatiotemporal model. We utilized liquid chromatography with high-resolution mass spectrometry. We used generalized linear models to test for associations between metabolomic features and PM2.5 exposures after adjusting for potential confounders. Significant features (P < 0.005) were used for pathway analysis and metabolite identification. Results: We identified 17 pathways related to amino acid, lipid, energy, and nutrient metabolism that were solely associated with acute PM2.5 exposure. Fifteen pathways, mostly, pro-inflammatory, anti-inflammatory, amino acid, and energy metabolism, were solely associated with long-term PM2.5 exposure. Seven pathways were associated with the majority of exposure windows and were mostly related to anti-inflammatory and lipid metabolism. Among the significant features, we confirmed seven metabolites with level-1 evidence. Conclusions: We identified serum metabolites and metabolic pathways uniquely associated with acute versus chronic PM2.5 exposure. These different biologic pathways may help explain differences in disease states when investigating different lengths of PM2.5 exposure.