Abstract Body
Background/Aim: Periconception air pollution exposure has been linked with diminished fertility, adverse birth outcomes, and neurodevelopmental disorders. Identifying the metabolic changes induced by air pollution exposure among reproductive-aged women could enhance our understanding of the biological pathways underlying air pollution’s reprotoxicity. Thus, our objective was to identify metabolic alterations associated with periconception air pollution exposure in women using a metabolome-wide association study. Methods: Our study included 200 women undergoing in vitro fertilization (IVF) at a fertility center in Boston, Massachusetts (2005-2015). Women provided blood samples during controlled ovarian stimulation and untargeted metabolic profiling was conducted on the serum samples using liquid chromatography with ultra-high-resolution mass spectrometry. Spatiotemporal models estimated residence-based daily nitrogen dioxide (NO2), ozone (O3), and fine particulate (PM2.5) concentrations in the 3 months prior to starting IVF. We evaluated associations between each air pollutant and each metabolic feature using linear regression adjusted for age, BMI, education level, smoking status, and average temperature. Pathway analyses were employed to identify biological pathways related to air pollution exposure. Results: From the negative and positive ionization modes, 10,803 and 12,968 metabolic features were extracted, respectively. Higher exposure to NO2, O3, and PM2.5 was associated with 80, 35, and 246 features, respectively, after controlling for false discovery rate. Across all three pollutants, no common feature was significantly altered; however, higher exposure to NO2, O3, and PM2.5 resulted in perturbations in the glycine, serine, alanine and threonine and linoleate pathways and to a lesser extent in the leukotriene, urea cycle/amino group vitamin E, and prostaglandin formation from arachidonate pathways. Conclusions: In this cross-sectional study, periconception air pollution exposures were correlated with a variety of metabolic pathways such as amino acid metabolism, inflammation, and oxidative stress. Future studies should determine whether these pathways mediate associations between air pollution and couple fertility.
