Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage
Autor: | Nancy Côté, Serge McGraw, Ayelet Ziv-Gal, Donovan Chan, Jacquetta M. Trasler, Sarah Kimmins, Astrid Deschênes, Janice L. Bailey, Mathieu Dalvai, Marie-Pier Scott-Boyer, Clotilde Maurice, Arnaud Droit, Jodi A. Flaws, Romain Lambrot |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
QH301-705.5
Health Toxicology and Mutagenesis Physiology Intrauterine growth restriction 010501 environmental sciences Biology 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Article 03 medical and health sciences Genetics medicine transgenerational Epigenetics Biology (General) 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Pregnancy persistent organic pollutants (POPs) urogenital system sperm methylome Epigenome medicine.disease Sperm Paternal Exposure Inuit DNA methylation intergenerational paternal transmission Gestation Medicine epigenetic |
Zdroj: | Epigenomes Volume 5 Issue 2 Epigenomes, Vol 5, Iss 10, p 10 (2021) |
ISSN: | 2075-4655 |
DOI: | 10.3390/epigenomes5020010 |
Popis: | 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. |
Databáze: | OpenAIRE |
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