PM2.5 exposure during pregnancy is associated with altered placental expression of lipid metabolic genes in a US birth cohort

• Type of Material: Article
• Authors: K Kaur, New York University; C Lesseur, Icahn School of Medicine at Mount Sinai; MA Deyssenroth, Columbia University; I Kloog, Ben Gurion University; JD Schwartz, Columbia University; Carmen Marsit, Emory University; Jia Chen, Icahn School of Medicine at Mount Sinai
• Language: English
• Date: 2022-03-08
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envres.2022.113066
• Title of Journal or Parent Work: ENVIRONMENTAL RESEARCH
• Volume: 211
• Start Page: 113066
• End Page: 113066
• Grant/Funding Information: This study was supported by the NIEHS-NIH R24ES028507 fund for RICHS. The Mount Sinai Transdisciplinary Center on Early Environmental Exposures NIEHS P30ES023515 and P30ES109776. The NIEHS 2T32ES007324-16 funded K. Kaur. The authors retain responsibility for the content, it does not necessarily the official views of the National Institutes of Health.
• Keywords: Science & Technology; Placenta; MARKERS; WEIGHT; PARTICULATE MATTER EXPOSURE; FETAL-GROWTH; Environmental Sciences; NORTHEASTERN; Pregnancy; Air pollution; Metabolism; ONSET; <p>PM2.5</p>; SEX; AMBIENT AIR-POLLUTION; Sex differences; Life Sciences & Biomedicine; Public, Environmental & Occupational Health; PARTICLES; MODEL; Environmental Sciences & Ecology
• Research Categories: Environmental Sciences; Health Sciences, Public Health

Abstract

Inhalation of ambient PM2.5, shown to be able to cross the placenta, has been linked to adverse obstetric and postnatal metabolic health outcomes. The placenta regulates fetal growth and influences postnatal development via fetal programming. Placental gene expression may be influenced by intrauterine exposures to PM2.5. Herein, we explore whether maternal PM2.5 exposure during pregnancy alters placental gene expression related to lipid and glucose metabolism in a U.S. birth cohort, the Rhode Island Child Health Study (RICHS). Average PM2.5 exposure level was estimated linking residential addresses and satellite data across the three trimesters using spatio-temporal models. Based on Gene Ontology annotations, we curated a list of 657 lipid and glucose metabolism genes. We conducted a two-staged analysis by leveraging placental RNA-Seq data from 148 subjects to identify top dysregulated metabolic genes associated with PM2.5 (Phase I) and then validated the results in placental samples from 415 participants of the cohort using RT-qPCR (Phase II). Associations between PM2.5 and placental gene expression were explored using multivariable linear regression models in the overall population and in sex-stratified analyses. The average level of PM2.5 exposure across pregnancy was 8.0μg/m3, which is below the national standard of 12μg/m3. Phase I revealed that expression levels of 32 out of the curated list of 657 genes were significantly associated with PM2.5 exposure (FDR P<0.01), 28 genes showed differential expression modified by sex of the infant. Five of these genes (ABHD3, ATP11A, CLTCL1, ST6GALNAC4 and PSCA) were validated using RT-qPCR. Associations were stronger in placentas from male births compared to females, indicating a sex-dependent effect. These genes are involved in inflammation, lipid transport, cell-cell communication or cell invasion. Our results suggest that gestational PM2.5 exposure may alter placental metabolic function. However, whether it confers long-term programming effects postnatally, especially in a sex-specific matter, warrants further studies.