ИСТИНА

Background: Animal data have demonstrated that the sperm epigenome is sensitive to endocrine disrupting compounds (EDCs) at specific windows of development. We examined the association of peripubertal dioxin exposure with profiles of DNA methylation in sperm collected in young adulthood. Methods: The Russian Children’s Study (RCS) is a prospective cohort of 516 boys who were enrolled at 8 to 9 years of age and resided in Chapaevsk, between 2003-2005. Most toxic dioxin congener, TCDD, was measured at the CDC, USA in serum collected at ages 8-9. We randomly selected 4 subjects with highest and 4 with lowest peripubertal TCDD levels who provided semen samples at ages 18-19. Libraries for whole genome bisulfite sequencing (WGBS) were constructed using TruSeq DNA methylation kit (Illumina). After SNP removal, differential methylated regions (DMRs) were identified via MethPipe package with the following parameters: ≥ 5x coverage depth, ≥ 3 CpGs, ≥ 10% methylation change and q value < 0.05. Results: We achieved an average of 136 million uniquely mapped reads per sample with an average coverage depth of 4X. We identified 142 DMRs that distinguished low and high peripubertal TCDD exposure. Enrichment analyses included terms for alternative splicing and cell membrane. Conclusion: To our knowledge, this is the first study to examine the impact of child dioxin exposure to persistent EDCs on adult sperm epigenome in humans. Funding: RSF #14-45-00065; for parent RCS - US EPA #R82943701 and NIEHS #R01 ES014370 and #P30 ES000002.