J Richard Pilsner1, Alex Shershebnev2, Yulia A Medvedeva3, Alexander Suvorov4, Haotian Wu5, Andrey Goltsov6, Evgeny Loukianov7, Tatiana Andreeva8, Fedor Gusev9, Andrey Manakhov10, Luidmila Smigulina11, Maria Logacheva12, Victoria Shtratnikova13, Irina Kuznetsova14, Peter Speranskiy-Podobed15, Jane S Burns16, Paige L Williams17, Susan Korrick18, Mary M Lee19, Evgeny Rogaev20, Russ Hauser21, Oleg Sergeyev22. 1. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA, 01003, USA. Electronic address: rpilsner@umass.edu. 2. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA, 01003, USA. Electronic address: ashershebnev@gmail.com. 3. Institute of Bioengineering, Research Center of Biotechnology Russian Academy of Sciences, 60 let Oktjabrja pr-t, 7, Bld. 1, 117312, Moscow, Russia; Department of Computational Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: ju.medvedeva@gmail.com. 4. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA, 01003, USA. Electronic address: asuvorov@schoolph.umass.edu. 5. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA, 01003, USA. Electronic address: haotianw@umass.edu. 6. Department of Molecular Genetics, Research Center for Obstetrics, Gynecology and Perinatology, 4 Oparin St., 117997, Moscow, Russia; Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: andrey.goltsov@gmail.com. 7. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: loukiaev@yandex.ru. 8. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: an_tati@mail.ru. 9. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: gusevfe@gmail.com. 10. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: andrey-manakhov@yandex.ru. 11. Chapaevsk Medical Association, 3a Meditsinskaya st., 446100, Chapaevsk, Samara region, Russia. Electronic address: chapmedass@samtel.ru. 12. A.N. Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory, House 1, Building 40, 119992, Moscow, Russia; Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, 143028, Moscow, Russia. Electronic address: maria.log@gmail.com. 13. A.N. Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory, House 1, Building 40, 119992, Moscow, Russia; Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, 143028, Moscow, Russia. Electronic address: vtosha@yandex.ru. 14. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: irakuzn@yahoo.com. 15. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia. Electronic address: ps.podobed@gmail.com. 16. Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. Electronic address: jburns@hsph.harvard.edu. 17. Department of Biostatistics, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. Electronic address: paige@sdac.harvard.edu. 18. Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA. Electronic address: susan.korrick@channing.harvard.edu. 19. Pediatric Endocrine Division, Department of Pediatrics, University of Massachusetts Medical School, 55 N Lake Avenue, Worcester, MA, 01655, USA. Electronic address: mary.lee@umassmemorial.org. 20. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, 01604 Worcester, MA, USA. Electronic address: rogaev@vigg.ru. 21. Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. Electronic address: rhauser@hsph.harvard.edu. 22. Department of Genomics and Human Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina St., 119991, Moscow, Russia; Chapaevsk Medical Association, 3a Meditsinskaya st., 446100, Chapaevsk, Samara region, Russia; A.N. Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory, House 1, Building 40, 119992, Moscow, Russia. Electronic address: olegsergeyev1@yandex.ru.
Abstract
BACKGROUND: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown. OBJECTIVE: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood. METHODS: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age. WGBS of sperm was conducted to identify differentially methylated regions (DMR) between highest (n = 4) and lowest (n = 4) peripubertal TCDD groups. RESULTS: We found 52 DMRs that distinguished lowest and highest peripubertal serum TCDD concentrations. One of the top scoring networks, "Cellular Assembly and Organization, Cellular Function and Maintenance, Carbohydrate Metabolism", identified estrogen receptor alpha as its central regulator. CONCLUSION: Findings from our limited sample size suggest that peripubertal environmental exposures are associated with sperm DNA methylation in young adults.
BACKGROUND: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown. OBJECTIVE: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood. METHODS: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age. WGBS of sperm was conducted to identify differentially methylated regions (DMR) between highest (n = 4) and lowest (n = 4) peripubertal TCDD groups. RESULTS: We found 52 DMRs that distinguished lowest and highest peripubertal serum TCDD concentrations. One of the top scoring networks, "Cellular Assembly and Organization, Cellular Function and Maintenance, Carbohydrate Metabolism", identified estrogen receptor alpha as its central regulator. CONCLUSION: Findings from our limited sample size suggest that peripubertal environmental exposures are associated with sperm DNA methylation in young adults.
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