ИСТИНА

Background/Aim. Exposures to endocrine disrupting chemicals during critical windows of testicular development and spermatogenesis may be related to poorer semen parameters and altered sperm DNA methylation. We evaluated the association of peripubertal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentration with semen parameters and sperm epigenetic markers. Methods. The Russian Children’s Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided blood samples for analysis for TCDD. Subjects who reached sexual maturity and were at least 18 years of age were invited to provide two semen samples approximately one week apart. Among these, 133 young men provided 256 samples, which were analyzed for volume, sperm concentration, and motility. Whole-genome bisulfite sequencing of sperm was conducted to identify differentially methylated regions (DMR) between groups of selected subjects with highest (n=4, 95th -99th percentiles) and lowest (n=4, level below limit of detection) peripubertal serum TCDD concentrations. Results. The median (range) for TCDD was 2.9 (0.4-12.1) pg/g lipid. The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29% (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. The mean (SD) methylation across all CpG sites was significantly lower in the selected highest peripubertal serum TCDD group compared to the selected lowest group (49.1 ± 4.9% and 61.9 ± 5.2%, respectively; t-test, p = 0.01). We found 52 DMRs that distinguished two serum TCDD groups. One of the top scoring networks, “Cellular Assembly and Organization, Cellular Function and Maintenance, Carbohydrate Metabolism”, identified estrogen receptor alpha (ESR1) as its central regulator. Conclusions. Our study is the first to suggest that peripubertal environmental exposures may be associated with subsequent poorer semen parameters and sperm methylation profiles in young adults.