Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian 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.

A 29.5 kDa heat-modifiable major outer membrane protein of Rickettsia prowazekii, putative virulence factor, is a peptidyl-prolyl cis/trans isomerase.

Allelic genes from three Rickettsia prowazekii strains encoding parvulin-like protein (Plp), a heat-modifiable 29.5 kDa major outer membrane protein, were earlier cloned into expression vector pQE 30. In this work, recombinant proteins were overproduced in E. coli, purified, and found to exhibit an expected peptidyl-prolyl cis/trans isomerase activity of a parvulin type in vitro with oligopeptide substrates. Native polypeptide of prototype virulent Breinl strain is known to differ by SDS-PAGE mobility from those of both vaccine Madrid E and virulent EVir isolates. Being different in electrophoretic behavior, heat-unmodified forms of the three strains were shown to migrate apart from lipopolysaccharides. A EVir Plp gene was sequenced, and deduced protein sequence was found to be identical to previously published Breinl and Madrid E. Present data indicate that unknown post-translational modification(s) in rickettsiae are responsible for both interstrain difference and heat-modifiability of Plp.