Role of epigenetic transgenerational inheritance in generational toxicology

Abstract

Many environmental toxicants have been shown to be associated with the transgenerational inheritance of increased disease susceptibility. This review describes the generational toxicity of some of these chemicals and their role in the induction of epigenetic transgenerational inheritance of disease. Epigenetic factors include DNA methylation, histone modifications, retention of histones in sperm, changes to chromatin structure, and expression of non-coding RNAs. For toxicant-induced epigenetic transgenerational inheritance to occur, exposure to a toxicant must result in epigenetic changes to germ cells (sperm or eggs) since it is the germ cells that carry molecular information to subsequent generations. In addition, the epigenetic changes induced in transgenerational generation animals must cause alterations in gene expression in these animals’ somatic cells. In some cases of generational toxicology, negligible changes are seen in the directly exposed generations, but increased disease rates are seen in transgenerational descendants. Governmental policies regulating toxicant exposure should take generational effects into account. A new approach that takes into consideration generational toxicity will be needed to protect our future populations.

Impact of Endocrine Disruptors upon Non-Genetic Inheritance

“…Exposure to the organochlorine insecticide chlordecone increases prostatic epithelial neoplasia in F1 and F3 mice, associated with alterations in histone H3K4me3 [ 24 ]. Histone modifications are epigenetic marks that can be transmitted to the offspring [ 25 ].…”

Developmental toxicant exposures and sex-specific effects on epigenetic programming and cardiovascular health across generations

“…The second wave of reprogramming occurs in the fetal primordial germ cells, in which sex and parent of origin-specific epigenetic patterning are established [ 67 ]. Environmental disruptions in the normal epigenetic patterning in germ cells that are not corrected during the development of the future generation may result in multi and transgenerational effects [ 68 ]. In a pregnant (F0) individual, toxicant-induced epigenetic changes may occur in their somatic and germ cells, as well as in the somatic and primordial germ cells of the developing fetus ( Fig.…”

“…In a pregnant (F0) individual, toxicant-induced epigenetic changes may occur in their somatic and germ cells, as well as in the somatic and primordial germ cells of the developing fetus ( Fig. 1 ) [ 68 ]. Toxicant exposure-induced effects occurring in the offspring (F1) and grand offspring (F2) generations are termed multigenerational effects, as F0 and F1 generations receive direct exposure during the pregnancy, and the primordial germ cells of the F2 generation are also directly exposed ( Fig.…”

“…Toxicant exposure-induced effects occurring in the offspring (F1) and grand offspring (F2) generations are termed multigenerational effects, as F0 and F1 generations receive direct exposure during the pregnancy, and the primordial germ cells of the F2 generation are also directly exposed ( Fig. 1 ) [ 68 ]. In contrast, transgenerational epigenetic inheritance refers to the transmission of environmental effects to future generations that did not receive the exposure directly through embryonic development or germ cells, i.e.…”

Impact of in Utero Rat Exposure to 17Alpha-Ethinylestradiol or Genistein on Testicular Development and Germ Cell Gene Expression

“…This suggests that treatment during gestation may have altered the regulatory mechanisms of gene expression in gonocytes, inducing changes in transcript levels in more differentiated germ cells at PND5. This could be due to genomic imprinting as suggested by others ( Nilsson et al, 2022 ). Indeed, the window of exposure also corresponds to the time of epigenetic reprogramming in the mammalian male germline, when there is near complete erasure of DNA methylation (DNAme), followed by de novo DNAme.…”