Serum dioxin and DNA methylation in the sperm of operation ranch hand veterans exposed to Agent Orange
Autor: | Edward Dere, Melissa Eliot, E. Andres Houseman, Susan M. Huse, Matthew Rae Rytel, Devin C. Koestler, Kim Boekelheide, Karl T. Kelsey, Rondi A. Butler |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Health Toxicology and Mutagenesis Semen 010501 environmental sciences Biology Dioxins 01 natural sciences Vietnam Conflict Andrology 03 medical and health sciences chemistry.chemical_compound lcsh:RC963-969 Agent Orange Humans Prospective Studies Epigenetics Aged Veterans 030304 developmental biology 0105 earth and related environmental sciences Aged 80 and over Dioxin 0303 health sciences DNA methylation Herbicides Research lcsh:Public aspects of medicine Public Health Environmental and Occupational Health lcsh:RA1-1270 Environmental Exposure Methylation Middle Aged Spermatozoa Sperm United States chemistry CpG site lcsh:Industrial medicine. Industrial hygiene Environmental Pollutants Genomic imprinting |
Zdroj: | Environmental Health, Vol 18, Iss 1, Pp 1-11 (2019) Environmental Health |
Popis: | Background Exposure to the herbicide Agent Orange during the Vietnam War was widespread and is associated with numerous adverse health outcomes. A continuing concern of veterans is the possibility that exposure to the dioxin-containing herbicide might induce adverse reproductive outcomes. We sought to assess whether exposure to Agent Orange in Vietnam was associated with changes in DNA methylation in sperm in a subset of Vietnam veterans who participated in the Air Force Health Study (AFHS). Methods We studied 37 members of the AFHS chosen to have no, low, medium or high exposure to Agent Orange, based upon serum dioxin levels obtained during a series of examinations. DNA from stored semen was extracted and DNA methylation assessed on the Illumina 450 K platform. Results Initial epigenome-wide analysis returned no loci that survived control for false discovery. However, the TEAD3 gene had four different CpG sites that showed loss of DNA methylation associated with dioxin exposure. Analysis assessing regional DNA methylation changes revealed 36 gene regions, including the region of the imprinted gene H19 to have altered DNA methylation associated with high exposure compared to the low exposure group. Additional comparison of our data with sperm DNA methylation data from Russian boys exposed to dioxin found an additional 5 loci that were altered in both studies and exhibited a consistent direction of association. Conclusions Studying a small number of sperm samples from veterans enrolled in the AFHS, we did not find evidence of significant epigenome-wide alterations associated with exposure to Agent Orange. However, additional analysis showed that the H19 gene region is altered in the sperm of Agent Orange-exposed Ranch Hand veterans. Our study also replicated several findings of a prior study of dioxin-exposed Russian boys. These results provide additional candidate loci for further investigation and may have implications for the reproductive health of dioxin-exposed individuals. |
Databáze: | OpenAIRE |
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