Early-life exposure to environmental contaminants perturbs the sperm epigenome and induces negative pregnancy outcomes for three generations via the paternal lineage

Maurice, C, Dalvai, M, Lambrot, R, Deschênes, A, Scott-Boyer, MP, McGraw, S, Chan, D, Côté, N, Ziv-Gal, A, Flaws, JA, Droit, A, Trasler, J, Kimmins, S, Bailey, JL (June 2021) Early-life exposure to environmental contaminants perturbs the sperm epigenome and induces negative pregnancy outcomes for three generations via the paternal lineage. Epigenomes, 5 (2). p. 10. ISSN 2075-4655

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Abstract

Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics diseases & disorders > pregnancy
CSHL Authors:	Deschenes, Astrid
Communities:	CSHL labs > Tuveson lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	1 June 2021
Date Deposited:	07 Jul 2021 13:15
Last Modified:	25 Jan 2024 15:21
PMCID:	PMC8594730
Related URLs:	PubMed
URI:	https://repository.cshl.edu/id/eprint/40252

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