Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality

• Type of Material: Article
• Authors: Sueyoun Hwang, Emory University; Robert B Hood, Emory University; Russ Hauser, Harvard T.H. Chan School of Public Health; Joel Schwartz, Harvard T.H. Chan School of Public Health; Francine Laden, Harvard T.H. Chan School of Public Health; Dean Jones, Emory University; Donghai Liang, Emory University; Audrey Gaskins, Emory University
• Language: English
• Date: 2022-11-01
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 The Author(s). Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envint.2022.107552
• Title of Journal or Parent Work: ENVIRONMENT INTERNATIONAL
• Volume: 169
• Start Page: 107552
• End Page: 107552
• Grant/Funding Information: This publication was also made possible by U.S. Environmental Protection Agency (U.S. EPA): RD-834798 and RD-83587201. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the U.S. EPA. Further, U.S. EPA does not endorse the purchase of any commercial products or services mentioned in the publication.; Supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS). The study was also supported by HERCULES through the NIEHS (P30 ES019776).
• Keywords: FERTILITY; Ovary; BENZO(A)PYRENE; HIGH-RESOLUTION METABOLOMICS; Life Sciences & Biomedicine; Metabolomics; HYPOXANTHINE; FINE PARTICULATE MATTER; Science & Technology; Environmental Sciences & Ecology; Fertility; MATURATION; Assisted reproduction; IMPACT; Environmental Sciences; MASS-SPECTROMETRY; EXPOSURE; Follicular fluid; Air pollution; MODEL

Abstract

Background and aim: Our objective was to use metabolomics in a toxicological-relevant target tissue to gain insight into the biological processes that may underlie the negative association between air pollution exposure and oocyte quality. Methods: Our study included 125 women undergoing in vitro fertilization at an academic fertility center in Massachusetts, US (2005–2015). A follicular fluid sample was collected during oocyte retrieval and untargeted metabolic profiling was conducted using liquid chromatography with ultra-high-resolution mass spectrometry and two chromatography columns (C18 and HILIC). Daily exposure to nitrogen dioxide (NO2), ozone, fine particulate matter, and black carbon was estimated at the women's residence using spatiotemporal models and averaged over the period of ovarian stimulation (2-weeks). Multivariable linear regression models were used to evaluate the associations between the air pollutants, number of mature oocytes, and metabolic feature intensities. A meet-in-the-middle approach was used to identify overlapping features and metabolic pathways. Results: Of the air pollutants, NO2 exposure had the largest number of overlapping metabolites (C18: 105; HILIC: 91) and biological pathways (C18: 3; HILIC: 6) with number of mature oocytes. Key pathways of overlap included vitamin D3 metabolism (both columns), bile acid biosynthesis (both columns), C21-steroid hormone metabolism (HILIC), androgen and estrogen metabolism (HILIC), vitamin A metabolism (HILIC), carnitine shuttle (HILIC), and prostaglandin formation (C18). Three overlapping metabolites were confirmed with level-1 or level-2 evidence. For example, hypoxanthine, a metabolite that protects against oxidant-induced cell injury, was positively associated with NO2 exposure and negatively associated with number of mature oocytes. Minimal overlap was observed between the other pollutants and the number of mature oocytes. Conclusions: Higher exposure to NO2 during ovarian stimulation was associated with many metabolites and biologic pathways involved in endogenous vitamin metabolism, hormone synthesis, and oxidative stress that may mediate the observed associations with lower oocyte quality.