Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands

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...

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Autores principales:	Allison Kupsco, Jenny Jyoung Lee, Diddier Prada, Damaskini Valvi, Lisa Hu, Maria Skaalum Petersen, Brent A. Coull, Pal Weihe, Philippe Grandjean, Andrea A. Baccarelli
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Extracellular vesicles microRNA Persistent organic pollutants Perfluoroalkyl substances Mercury Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/c70d9f441c9c48b2ac0753397b7ac66a
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spelling	oai:doaj.org-article:c70d9f441c9c48b2ac0753397b7ac66a2021-11-22T04:16:56ZMarine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands0160-412010.1016/j.envint.2021.106986https://doaj.org/article/c70d9f441c9c48b2ac0753397b7ac66a2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0160412021006115https://doaj.org/toc/0160-4120Background/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 (ΣPCBs) 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 ΣPCBs 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.Allison KupscoJenny Jyoung LeeDiddier PradaDamaskini ValviLisa HuMaria Skaalum PetersenBrent A. CoullPal WeihePhilippe GrandjeanAndrea A. BaccarelliElsevierarticleExtracellular vesiclesmicroRNAPersistent organic pollutantsPerfluoroalkyl substancesMercuryEnvironmental sciencesGE1-350ENEnvironment International, Vol 158, Iss , Pp 106986- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Extracellular vesicles microRNA Persistent organic pollutants Perfluoroalkyl substances Mercury Environmental sciences GE1-350
spellingShingle	Extracellular vesicles microRNA Persistent organic pollutants Perfluoroalkyl substances Mercury Environmental sciences GE1-350 Allison Kupsco Jenny Jyoung Lee Diddier Prada Damaskini Valvi Lisa Hu Maria Skaalum Petersen Brent A. Coull Pal Weihe Philippe Grandjean Andrea A. Baccarelli Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
description	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 (ΣPCBs) 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 ΣPCBs 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.
format	article
author	Allison Kupsco Jenny Jyoung Lee Diddier Prada Damaskini Valvi Lisa Hu Maria Skaalum Petersen Brent A. Coull Pal Weihe Philippe Grandjean Andrea A. Baccarelli
author_facet	Allison Kupsco Jenny Jyoung Lee Diddier Prada Damaskini Valvi Lisa Hu Maria Skaalum Petersen Brent A. Coull Pal Weihe Philippe Grandjean Andrea A. Baccarelli
author_sort	Allison Kupsco
title	Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
title_short	Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
title_full	Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
title_fullStr	Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
title_full_unstemmed	Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands
title_sort	marine pollutant exposures and human milk extracellular vesicle-micrornas in a mother-infant cohort from the faroe islands
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/c70d9f441c9c48b2ac0753397b7ac66a
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Marine pollutant exposures and human milk extracellular vesicle-microRNAs in a mother-infant cohort from the Faroe Islands

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