Transgenerational epigenetic programming of the embryonic testis transcriptome

Abstract

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination appears to promote an epigenetic reprogramming of the male germ line that is associated with transgenerational adult-onset disease states. Transgenerational effects on the embryonic day 16 (E16) testis demonstrated reproducible changes in the testis transcriptome for multiple generations (F1-F3). The expression of 196 genes was found to be influenced, with the majority of gene expression being decreased or silenced. Dramatic changes in the gene expression of methyltransferases during gonadal sex determination were observed in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority returned to control-generation levels by the F3 generation. The most dramatic effects were on the germ-line-associated Dnmt3A and Dnmt3L isoforms. Observations demonstrate that an embryonic exposure to vinclozolin appears to promote an epigenetic reprogramming of the male germ line that correlates with transgenerational alterations in the testis transcriptome in subsequent generations.

RNA regulation of epigenetic processes

“…(112) The phenomenon may also be induced by miRNAs (112) and environmental parameters. (113)(114)(115) Intriguingly there is increasing evidence that RNA-coupled DNA 'repair' can also occur in eukaryotes, (94,116) suggesting that RNA can direct both epigenetic and genetic modifications and that there is a much more dynamic interplay between genomes and the environment than previously envisioned.…”

Effects of endocrine disruptors on imprinted gene expression in the mouse embryo

“…51 Hormones are known regulators of transcription through their effect on DNA methylation and chromatin composition. 52,53 Since EDs can affect DNA methylation patterns 33,54,55 and gene expression, [56][57][58][59][60] it is hypothesized that these hormonelike chemicals can alter the reciprocal epigenetic states of the two parental chromosomes at imprinted genes or their DMRs and those epigenetic changes would alter the allele-specific expression in the embryonic or extraembryonic organs. To test this hypothesis we generated multiplex allele-specific assays and measured the effects of BPA, VZ and DEHP on the maintenance of imprinted gene expression of a representative set of imprinted transcripts in the embryo and in extraembryonic organs after in utero exposure to these chemicals.…”

Population epigenetics, ecotoxicology and human diseases

“…В мужском F1 потомстве этих крыс наблюдали пониженный сперма-тогенез. Эти явления наблюдались в трех последующих мужских, не подвергавшихся воздействию поколениях (F2 до F4) и были связанны с аномальным метилирова-нием ДНК в спермиях (Anway et al, 2008). Подобным образом воздействие винклозолином на беременных са-мок F0 вызывало повышение частоты опухолеобразова-ния и увеличение частоты других различных заболеваний (например, почек и иммунной системы) в процессе ста-рения самцов поколений от F1 до F4 (Anway et al, 2006;Stouder et al, 2010).…”