transgenerational epigenetics

Parental exposure to drugs of abuse induces changes in the germline that can be transmitted across subsequent generations, resulting in enduring effects on gene expression and behavior. This transgenerational inheritance involves a dynamic interplay of environmental, genetic, and epigenetic factors that impact an individual's vulnerability to neuropsychiatric disorders. This chapter aims to summarize recent research into the mechanisms underlying the inheritance of gene expression and phenotypic patterns associated with exposure to drugs of abuse, with an emphasis on cocaine...

A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno-miR-184 and rno-miR-141-3p in the ventral prostate (VP) of offspring. Here, rno-miR-184 and rno-miR-141-3 expressions were obtained by RT-qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets...

Drug addiction is characterized by maladaptive neural plasticity, particularly in vulnerable individuals exposed to drugs of abuse. Epigenetic factors include environmental influences, events during development, and stress adaptations, which seem to play an important role in the neuropathogenesis of drug addiction. This critical review hypothesizes that epigenetic modulation increases an individual's susceptibility to opiate addiction in three key areas of epigenetic study: developmental, stress-related, and transgenerational effects...

Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited. Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene Khdc3 have hepatic metabolic defects that persist over multiple generations. We find that genetically wild type females descended from Khdc3 mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages...

That certain preconceptual paternal exposures reprogram the developmental phenotypic plasticity in future generation(s) has conceptualized the "paternal programming of offspring health" hypothesis. This transgenerational effect is transmitted primarily through sperm epigenetic mechanisms-DNA methylation, non-coding RNAs (ncRNAs) and associated RNA modifications, and histone modifications-and potentially through non-sperm-specific mechanisms-seminal plasma and circulating factors-that create 'imprinted' memory of ancestral information...

Epigenetic changes in sexually reproducing animals may be transmitted usually only through a few generations. Here we discovered a case where epigenetic change lasts 40 generations. This epigenetic phenomenon occurs in the short antennae (sa) mutation of the flour moth (Ephestia kuehniella). We demonstrate that is probably determined by a small RNA (e.g., piRNA, miRNA, tsRNA) and transmitted in this way to subsequent generations through the male and female gametes. The observed epigenetic change cancels sa mutation and creates a wild phenotype (a moth that appears to have no mutation)...

Genomic imprinting-the non-equivalence of maternal and paternal genomes-is a critical process that has evolved independently in many plant and mammalian species1,2 . According to kinship theory, imprinting is the inevitable consequence of conflictive selective forces acting on differentially expressed parental alleles3,4 . Yet, how these epigenetic differences evolve in the first place is poorly understood3,5,6 . Here we report the identification and molecular dissection of a parent-of-origin effect on gene expression that might help to clarify this fundamental question...

INTRODUCTION: The ability to identify early epigenetic signatures underlying the inheritance of cardiovascular risk, including trans- and intergenerational effects, may help to stratify people before cardiac symptoms occur. METHODS: Prospective and retrospective cohorts and case-control studies focusing on DNA methylation and maternal/paternal effects were searched in Pubmed from 1997 to 2023 by using the following keywords: DNA methylation, genomic imprinting, and network analysis in combination with transgenerational/intergenerational effects...

Worldwide, diabetes mellitus represents a growing health problem. If it occurs during pregnancy, it can increase the risk of various abnormalities in early and advanced life stages of exposed individuals due to fetal programming occurring in utero. Studies have determined that maternal conditions interfere with the genotypes and phenotypes of offspring. Researchers are now uncovering the mechanisms by which epigenetic alterations caused by diabetes affect the expression of genes and, therefore, the development of various diseases...

Organisms are experiencing higher average temperatures and greater temperature variability because of anthropogenic climate change. Some populations respond to changes in temperature by shifting their ranges or adjusting their phenotypes via plasticity and/or evolution, while others go extinct. Predicting how populations will respond to temperature changes is challenging because extreme and unpredictable climate changes will exert novel selective pressures. For this reason, there is a need to understand the physiological mechanisms that regulate organismal responses to temperature changes...

Transgenerational epigenetic inheritance in mammals remains a controversial phenomenon. A recent study by Takahashi et al. provides evidence for this mode of inheritance in mice by using a CRISPR/Cas9-based epigenetic editing technique to modify DNA methylation levels at specific promoters and then demonstrating the inheritance of the gain in methylation in offspring. In this technical commentary, we argue that the method used in the original study inherently amplifies the likelihood of genetic changes that thereafter lead to the heritability of epigenetic changes...

The herbicide linuron can cause endocrine disrupting effects in Xenopus tropicalis frogs, including offspring that were never exposed to the contaminant. The mechanisms by which these effects are transmitted across generations need to be further investigated. Here, we examined transgenerational alterations of brain and testis DNA methylation profiles paternally inherited from grandfathers developmentally exposed to an environmentally relevant concentration of linuron. Reduced representation bisulfite sequencing (RRBS) revealed numerous differentially methylated regions (DMRs) in brain (3060 DMRs) and testis (2551 DMRs) of the adult male F2 generation...

AbstractNumerous empirical studies have witnessed an increase in meiotic recombination rate in response to physiological stress imposed by unfavorable environmental conditions. Thus, inherited plasticity in recombination rate is hypothesized to be evolutionarily advantageous in changing environments. Previous theoretical models proceeded from the assumption that organisms increase their recombination rate when the environment becomes more stressful and demonstrated the evolutionary advantage of such a form of plasticity...

Plant responses to abiotic stresses are dynamic, following the unpredictable changes of physical environmental parameters such as temperature, water and nutrients. Physiological and phenotypical responses to stress are intercalated by periods of recovery. An earlier stress can be remembered as 'stress memory' to mount a response within a generation or transgenerationally. The 'stress priming' phenomenon allows plants to respond quickly and more robustly to stressors to increase survival, and therefore has significant implications for agriculture...

BACKGROUND: Despite the increasing number of epigenomic studies in plants, little is known about the forces that shape the methylome in long-lived woody perennials. The Lombardy poplar offers an ideal opportunity to investigate the impact of the individual environmental history of trees on the methylome. RESULTS: We present the results of three interconnected experiments on Lombardy poplar. In the first experiment, we investigated methylome variability during a growing season and across vegetatively reproduced generations...

PURPOSE: Task Group 121 - Effects of ionizing radiation exposure in offspring and next generations - is a task group under the Committee 1 of the International Commission on Radiological Protection (ICRP), approved by the Main Commission on 18th November 2021. The main goals of Task Group 121 are to (1) review and update the scientific literature of relevance to radiation-related effects in the offspring of parent(s) exposed to ionizing radiation in both human and non-human biota; (2) to assess preconceptional and intrauterine effects of radiation exposure and related morbidity and mortality; and, (3) to provide advice about the level of evidence and how to consider these preconceptional and postconceptional effects in the system of radiological protection for humans and non-human biota...

Mercury (Hg) and vitamin A (VitA) are two environmental factors with potential health impacts, especially during pregnancy and early childhood. Fish and seafood may present elevated levels of methylmercury (MeHg), the major Hg derivative, and VitA. This study aimed to evaluate the transgenerational effects of exposure to MeHg and/or VitA on epigenetic and toxicological parameters in a Wistar rat model. Our findings revealed persistent toxicological effects in generations F1 and F2 following low/mild doses of MeHg and/or VitA exposure during dams' (F0) gestation and breastfeeding...

Clubroot caused by the protist Plasmodiophora brassicae is a major disease affecting cultivated Brassicaceae. Using a combination of QTL fine mapping, CRISPR/Cas9 validation and extensive analyses of DNA sequence and methylation patterns, we uncovered that the two adjacent neighboring NLR (nucleotide-binding and leucine-rich repeat) genes AT5G47260 and AT5G47280 cooperate in controlling broad-spectrum quantitative partial resistance to the root pathogen P. brassicae in Arabidopsis and that they are epigenetically regulated...

In recent years, there has been growing concern about the adverse effects of endocrine disrupting chemicals (EDCs) on male fertility. Epigenetic modification is critical for male germline development, and has been suggested as a potential mechanism for impaired fertility induced by EDCs. Bisphenol A (BPA) has been recognized as a typical EDC. BPA and its analogues, which are still widely used in various consumer products, have garnered increasing attention due to their reproductive toxicity and the potential to induce epigenetic alteration...

Endocrine-disrupting chemicals (EDCs) might contribute to the increase in female-specific cancers in Western countries. 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) is considered the "prototypical toxicant" to study EDCs' effects on reproductive health. Epigenetic regulation by small noncoding RNAs (sncRNAs), such as microRNAs (miRNA), is crucial for controlling cancer development. The aim of this study was to analyze transcriptional activity and sncRNA expression changes in the KGN cell line after acute (3 h) and chronic (72 h) exposure to 10 nM TCDD in order to determine whether sncRNAs' deregulation may contribute to transmitting TCDD effects to the subsequent cell generations (day 9 and day 14 after chronic exposure)...