PMID- 34991248 OWN - NLM STAT- MEDLINE DCOM- 20220110 LR - 20240412 IS - 1873-6750 (Electronic) IS - 0160-4120 (Print) IS - 0160-4120 (Linking) VI - 158 DP - 2022 Jan TI - Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands. PG - 106986 LID - S0160-4120(21)00611-5 [pii] LID - 10.1016/j.envint.2021.106986 [doi] AB - BACKGROUND/AIMS: Early life exposures to marine contaminants can adversely impact child health but modes of action are unclear. Human milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on child health. However, the role of marine pollutants on miRNA expression in milk EVs is unexplored. METHODS: We isolated EV RNA from 333 milk samples collected between 2 and 74 days postpartum from a Faroese birth cohort born 1997-2000 and sequenced 2083 miRNAs using a targeted library preparation method. We quantified five perfluoroalkyl substances (PFAS), pesticide metabolite p,p'-dichlorodiphenyldichloroethylene (DDE), and the sum of three major polychlorinated biphenyls (SigmaPCBs) in maternal serum at 34 weeks of gestation and maternal hair total mercury (Hg) at birth. We used negative binomial regressions to estimate associations between individual pollutants and 418 reliably expressed EV-miRNAs adjusted for potential confounders. We performed sparse principal components (PCs) analysis to derive the first four components of the EV-miRNA data and examined associations between pollutants and PCs using Bayesian kernel machine regression (BKMR). RESULTS: We observed no associations between pollutants and individual EV-miRNA expression after controlling the false discovery rate at 0.1. However, BKMR suggested that Hg was positively associated with PC1 and negatively associated with PC3, while SigmaPCBs was negatively associated with PC3, and two PFAS were associated with PC4. Exploration of PC loadings followed by pathway analyses suggested that miRNAs in PC1 (miR-200b-3p, miR-664a-3p, miR-6738-5p, miR-429, miR-1236-5p, miR-4464, and miR-30b-5p) may be related to Hg neurotoxicity, while remaining PCs require further research. CONCLUSIONS: Our findings suggest that groups of milk EV-miRNAs may better serve as environmental biomarkers than individual miRNAs. Future studies are needed to elucidate the role of milk EV-miRNAs in child health following prenatal exposures. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Kupsco, Allison AU - Kupsco A AD - Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10023, United States. Electronic address: ak4181@cumc.columbia.edu. FAU - Lee, Jenny Jyoung AU - Lee JJ AD - Department of Biostatistics, Harvard T.H Chan School of Public Health, Boston, MA, United States. FAU - Prada, Diddier AU - Prada D AD - Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10023, United States; Instituto Nacional de Cancerologia, San Fernando 22, Colonia Seccion XVI, Tlalpan, Mexico City 14080, Mexico. FAU - Valvi, Damaskini AU - Valvi D AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. FAU - Hu, Lisa AU - Hu L AD - Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10023, United States. FAU - Petersen, Maria Skaalum AU - Petersen MS AD - Department of Occupational Medicine and Public Health, The Faroese Hospital System, Torshavn, Faroe Islands; Center of Health Science, University of The Faroe Islands, Torshavn, Faroe Islands. FAU - Coull, Brent A AU - Coull BA AD - Department of Biostatistics, Harvard T.H Chan School of Public Health, Boston, MA, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States. FAU - Weihe, Pal AU - Weihe P AD - Department of Occupational Medicine and Public Health, The Faroese Hospital System, Torshavn, Faroe Islands; Center of Health Science, University of The Faroe Islands, Torshavn, Faroe Islands. FAU - Grandjean, Philippe AU - Grandjean P AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Environmental Medicine, University of Southern Denmark, Odense C, Denmark. FAU - Baccarelli, Andrea A AU - Baccarelli AA AD - Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY 10023, United States. LA - eng GR - R21 ES027087/ES/NIEHS NIH HHS/United States GR - T32 ES007142/ES/NIEHS NIH HHS/United States GR - P30 ES009089/ES/NIEHS NIH HHS/United States GR - R21 ES029328/ES/NIEHS NIH HHS/United States GR - R00 ES030749/ES/NIEHS NIH HHS/United States GR - P42 ES027706/ES/NIEHS NIH HHS/United States GR - K99 ES030749/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20211120 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Environmental Pollutants) RN - 0 (MIRN1236 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Bayes Theorem MH - Birth Cohort MH - Child MH - *Environmental Pollutants/toxicity MH - *Extracellular Vesicles MH - Female MH - Humans MH - Infant, Newborn MH - *MicroRNAs/genetics MH - Milk, Human MH - Mothers MH - Pregnancy PMC - PMC8742869 MID - NIHMS1759571 OTO - NOTNLM OT - Extracellular vesicles OT - Mercury OT - Perfluoroalkyl substances OT - Persistent organic pollutants OT - microRNA EDAT- 2022/01/08 06:00 MHDA- 2022/01/11 06:00 PMCR- 2023/01/01 CRDT- 2022/01/07 01:00 PHST- 2021/08/27 00:00 [received] PHST- 2021/10/29 00:00 [revised] PHST- 2021/11/15 00:00 [accepted] PHST- 2022/01/07 01:00 [entrez] PHST- 2022/01/08 06:00 [pubmed] PHST- 2022/01/11 06:00 [medline] PHST- 2023/01/01 00:00 [pmc-release] AID - S0160-4120(21)00611-5 [pii] AID - 10.1016/j.envint.2021.106986 [doi] PST - ppublish SO - Environ Int. 2022 Jan;158:106986. doi: 10.1016/j.envint.2021.106986. Epub 2021 Nov 20.