Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder
Environmental exposures to endocrine disrupting compounds (EDCs) such as the organochlorines have been linked with various diseases including neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder that is considered strongly genetic in origin due...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.929471/full |
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| author | Angela G. Maggio Henry T. Shu Henry T. Shu Benjamin I. Laufer Chongfeng Bi Yinglei Lai Janine M. LaSalle Valerie W. Hu |
| author_facet | Angela G. Maggio Henry T. Shu Henry T. Shu Benjamin I. Laufer Chongfeng Bi Yinglei Lai Janine M. LaSalle Valerie W. Hu |
| author_sort | Angela G. Maggio |
| collection | DOAJ |
| description | Environmental exposures to endocrine disrupting compounds (EDCs) such as the organochlorines have been linked with various diseases including neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder that is considered strongly genetic in origin due to its high heritability. However, the rapidly rising prevalence of ASD suggests that environmental factors may also influence risk for ASD. In the present study, whole genome bisulfite sequencing was used to identify genome-wide differentially methylated regions (DMRs) in a total of 52 sperm samples from a cohort of men from the Faroe Islands (Denmark) who were equally divided into high and low exposure groups based on their serum levels of the long-lived organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a primary breakdown product of the now banned insecticide dichlorodiphenyltrichloroethane (DDT). Aside from being considered a genetic isolate, inhabitants of the Faroe Islands have a native diet that potentially exposes them to a wide range of seafood neurotoxicants in the form of persistent organic pollutants (POPs). The DMRs were mapped to the human genome using Bismark, a 3-letter aligner used for methyl-seq analyses. Gene ontology, functional, and pathway analyses of the DMR-associated genes showed significant enrichment for genes involved in neurological functions and neurodevelopmental processes frequently impacted by ASD. Notably, these genes also significantly overlap with autism risk genes as well as those previously identified in sperm from fathers of children with ASD in comparison to that of fathers of neurotypical children. These results collectively suggest a possible mechanism involving altered methylation of a significant number of neurologically relevant ASD risk genes for introducing epigenetic changes associated with environmental exposures into the sperm methylome. Such changes may provide the potential for transgenerational inheritance of ASD as well as other disorders. |
| first_indexed | 2024-04-13T13:28:07Z |
| format | Article |
| id | doaj.art-4049fdc39ba74dbcb2ae582372ba4402 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T13:28:07Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-4049fdc39ba74dbcb2ae582372ba44022022-12-22T02:45:04ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.929471929471Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorderAngela G. Maggio0Henry T. Shu1Henry T. Shu2Benjamin I. Laufer3Chongfeng Bi4Yinglei Lai5Janine M. LaSalle6Valerie W. Hu7Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United StatesDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United StatesThe Johns Hopkins University, School of Medicine, Baltimore, MD, United StatesGenome Center, Perinatal Origins of Disparities Center, Environmental Health Sciences Center, Medical Microbiology and Immunology, MIND Institute, UC Davis School of Medicine, Davis, CA, United StatesDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United StatesDepartment of Statistics, The George Washington University, Washington, DC, United StatesGenome Center, Perinatal Origins of Disparities Center, Environmental Health Sciences Center, Medical Microbiology and Immunology, MIND Institute, UC Davis School of Medicine, Davis, CA, United StatesDepartment of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United StatesEnvironmental exposures to endocrine disrupting compounds (EDCs) such as the organochlorines have been linked with various diseases including neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder that is considered strongly genetic in origin due to its high heritability. However, the rapidly rising prevalence of ASD suggests that environmental factors may also influence risk for ASD. In the present study, whole genome bisulfite sequencing was used to identify genome-wide differentially methylated regions (DMRs) in a total of 52 sperm samples from a cohort of men from the Faroe Islands (Denmark) who were equally divided into high and low exposure groups based on their serum levels of the long-lived organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a primary breakdown product of the now banned insecticide dichlorodiphenyltrichloroethane (DDT). Aside from being considered a genetic isolate, inhabitants of the Faroe Islands have a native diet that potentially exposes them to a wide range of seafood neurotoxicants in the form of persistent organic pollutants (POPs). The DMRs were mapped to the human genome using Bismark, a 3-letter aligner used for methyl-seq analyses. Gene ontology, functional, and pathway analyses of the DMR-associated genes showed significant enrichment for genes involved in neurological functions and neurodevelopmental processes frequently impacted by ASD. Notably, these genes also significantly overlap with autism risk genes as well as those previously identified in sperm from fathers of children with ASD in comparison to that of fathers of neurotypical children. These results collectively suggest a possible mechanism involving altered methylation of a significant number of neurologically relevant ASD risk genes for introducing epigenetic changes associated with environmental exposures into the sperm methylome. Such changes may provide the potential for transgenerational inheritance of ASD as well as other disorders.https://www.frontiersin.org/articles/10.3389/fgene.2022.929471/fullendocrine disrupting compoundsDNA methylationspermFaroe Islandsautism |
| spellingShingle | Angela G. Maggio Henry T. Shu Henry T. Shu Benjamin I. Laufer Chongfeng Bi Yinglei Lai Janine M. LaSalle Valerie W. Hu Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder Frontiers in Genetics endocrine disrupting compounds DNA methylation sperm Faroe Islands autism |
| title | Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| title_full | Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| title_fullStr | Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| title_full_unstemmed | Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| title_short | Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| title_sort | elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder |
| topic | endocrine disrupting compounds DNA methylation sperm Faroe Islands autism |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.929471/full |
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