PMID- 34968297 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220101 IS - 2075-4655 (Electronic) IS - 2075-4655 (Linking) VI - 5 IP - 2 DP - 2021 May 1 TI - Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage. LID - 10.3390/epigenomes5020010 [doi] LID - 10 AB - 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. FAU - Maurice, Clotilde AU - Maurice C AUID- ORCID: 0000-0003-4120-4993 AD - Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Universite Laval, Quebec City, QC G1V 0A6, Canada. FAU - Dalvai, Mathieu AU - Dalvai M AD - Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Universite Laval, Quebec City, QC G1V 0A6, Canada. FAU - Lambrot, Romain AU - Lambrot R AD - Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, QC H9X 3V9, Canada. AD - Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada. FAU - Deschenes, Astrid AU - Deschenes A AD - Department of Molecular Medicine, Research Center of CHU of Quebec City, Universite Laval, Quebec City, QC G1V 4G, Canada. FAU - Scott-Boyer, Marie-Pier AU - Scott-Boyer MP AD - Department of Molecular Medicine, Research Center of CHU of Quebec City, Universite Laval, Quebec City, QC G1V 4G, Canada. FAU - McGraw, Serge AU - McGraw S AUID- ORCID: 0000-0002-3504-8253 AD - Research Center of CHU Sainte-Justine, Department of Biochemistry and Molecular Medicine, Universite de Montral, Montreal, QC H3T 1C5, Canada. FAU - Chan, Donovan AU - Chan D AD - Research Institute of the McGill University Health Centre, Montreal, QC H3Z 2Z3, Canada. AD - Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Montreal, QC H3Z 2Z3, Canada. FAU - Cote, Nancy AU - Cote N AUID- ORCID: 0000-0003-4062-3643 AD - Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Universite Laval, Quebec City, QC G1V 4G5, Canada. FAU - Ziv-Gal, Ayelet AU - Ziv-Gal A AUID- ORCID: 0000-0002-4748-5338 AD - Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA. FAU - Flaws, Jodi A AU - Flaws JA AUID- ORCID: 0000-0001-5579-9268 AD - Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA. FAU - Droit, Arnaud AU - Droit A AUID- ORCID: 0000-0001-7922-790X AD - Department of Molecular Medicine, Research Center of CHU of Quebec City, Universite Laval, Quebec City, QC G1V 4G, Canada. FAU - Trasler, Jacquetta AU - Trasler J AD - Research Institute of the McGill University Health Centre, Montreal, QC H3Z 2Z3, Canada. AD - Departments of Pediatrics, Human Genetics and Pharmacology & Therapeutics, McGill University, Montreal, QC H3Z 2Z3, Canada. FAU - Kimmins, Sarah AU - Kimmins S AD - Department of Animal Sciences, McGill University, Ste. Anne de Bellevue, Quebec, QC H9X 3V9, Canada. AD - Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada. FAU - Bailey, Janice L AU - Bailey JL AUID- ORCID: 0000-0002-5490-6946 AD - Research Centre on Reproduction and Intergenerational Health, Department of Animal Sciences, Universite Laval, Quebec City, QC G1V 0A6, Canada. LA - eng GR - PR-133831/Fonds de Recherche du Quebec - Nature et Technologies/ PT - Journal Article DEP - 20210501 PL - Switzerland TA - Epigenomes JT - Epigenomes JID - 101736595 PMC - PMC8594730 OTO - NOTNLM OT - Inuit OT - epigenetic OT - intergenerational OT - paternal transmission OT - persistent organic pollutants (POPs) OT - sperm methylome OT - transgenerational COIS- There are no conflict of interest prejudicing the impartiality of the research reported. EDAT- 2021/12/31 06:00 MHDA- 2021/12/31 06:01 PMCR- 2021/05/01 CRDT- 2021/12/30 17:14 PHST- 2021/03/22 00:00 [received] PHST- 2021/04/27 00:00 [accepted] PHST- 2021/12/30 17:14 [entrez] PHST- 2021/12/31 06:00 [pubmed] PHST- 2021/12/31 06:01 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - epigenomes5020010 [pii] AID - epigenomes-05-00010 [pii] AID - 10.3390/epigenomes5020010 [doi] PST - epublish SO - Epigenomes. 2021 May 1;5(2):10. doi: 10.3390/epigenomes5020010.