Length of PM_2.5exposure and alterations in the serum metabolome among women undergoing infertility treatment

Background: Both acute and chronic exposure to fine particulate matter (PM_2.5) have been linked to negative health outcomes. Studies have used metabolomics to describe the biological pathways linking PM_2.5with disease but have focused on a single exposure window. We compared alterations in the serum metabolome following various short-and long-Term PM_2.5exposures. 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. PM_2.5exposure 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 PM_2.5exposures 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 PM_2.5exposure. Fifteen pathways, mostly, pro-inflammatory, anti-inflammatory, amino acid, and energy metabolism, were solely associated with long-Term PM_2.5exposure. 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 PM_2.5exposure. These different biologic pathways may help explain differences in disease states when investigating different lengths of PM_2.5exposure.