Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior

Abstract Cadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models and humans suggests maternal Cd exposure negatively impacts neurodevelopment; how...

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Autores principales:	Kathleen M. Hudson, Emily Shiver, Jianshi Yu, Sanya Mehta, Dereje D. Jima, Maureen A. Kane, Heather B. Patisaul, Michael Cowley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ef5af741c9e54dcf84e1d71c3d38117c
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spelling	oai:doaj.org-article:ef5af741c9e54dcf84e1d71c3d38117c2021-12-02T15:08:11ZTranscriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior10.1038/s41598-021-95630-22045-2322https://doaj.org/article/ef5af741c9e54dcf84e1d71c3d38117c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95630-2https://doaj.org/toc/2045-2322Abstract Cadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models and humans suggests maternal Cd exposure negatively impacts neurodevelopment; however, the underlying molecular mechanisms are unclear. To address this, we utilized multiple -omics approaches in a mouse model of maternal Cd exposure to identify pathways altered in the developing brain. Offspring maternally exposed to Cd presented with enlarged brains proportional to body weights at birth and altered behavior at adulthood. RNA-seq in newborn brains identified exposure-associated increases in Hox gene and myelin marker expression and suggested perturbed retinoic acid (RA) signaling. Proteomic analysis showed altered levels of proteins involved in cellular energy pathways, hypoxic response, and RA signaling. Consistent with transcriptomic and proteomic analyses, we identified increased levels of retinoids in maternally-exposed newborn brains. Metabolomic analyses identified metabolites with significantly altered abundance, supportive of changes to cellular energy pathways and hypoxia. Finally, maternal Cd exposure reduced mitochondrial DNA levels in newborn brains. The identification of multiple pathways perturbed in the developing brain provides a basis for future studies determining the mechanistic links between maternal Cd exposure and altered neurodevelopment and behavior.Kathleen M. HudsonEmily ShiverJianshi YuSanya MehtaDereje D. JimaMaureen A. KaneHeather B. PatisaulMichael CowleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kathleen M. Hudson Emily Shiver Jianshi Yu Sanya Mehta Dereje D. Jima Maureen A. Kane Heather B. Patisaul Michael Cowley Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
description	Abstract Cadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models and humans suggests maternal Cd exposure negatively impacts neurodevelopment; however, the underlying molecular mechanisms are unclear. To address this, we utilized multiple -omics approaches in a mouse model of maternal Cd exposure to identify pathways altered in the developing brain. Offspring maternally exposed to Cd presented with enlarged brains proportional to body weights at birth and altered behavior at adulthood. RNA-seq in newborn brains identified exposure-associated increases in Hox gene and myelin marker expression and suggested perturbed retinoic acid (RA) signaling. Proteomic analysis showed altered levels of proteins involved in cellular energy pathways, hypoxic response, and RA signaling. Consistent with transcriptomic and proteomic analyses, we identified increased levels of retinoids in maternally-exposed newborn brains. Metabolomic analyses identified metabolites with significantly altered abundance, supportive of changes to cellular energy pathways and hypoxia. Finally, maternal Cd exposure reduced mitochondrial DNA levels in newborn brains. The identification of multiple pathways perturbed in the developing brain provides a basis for future studies determining the mechanistic links between maternal Cd exposure and altered neurodevelopment and behavior.
format	article
author	Kathleen M. Hudson Emily Shiver Jianshi Yu Sanya Mehta Dereje D. Jima Maureen A. Kane Heather B. Patisaul Michael Cowley
author_facet	Kathleen M. Hudson Emily Shiver Jianshi Yu Sanya Mehta Dereje D. Jima Maureen A. Kane Heather B. Patisaul Michael Cowley
author_sort	Kathleen M. Hudson
title	Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
title_short	Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
title_full	Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
title_fullStr	Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
title_full_unstemmed	Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
title_sort	transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ef5af741c9e54dcf84e1d71c3d38117c
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Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior

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