Inheritance of environment-induced phenotypic changes through epigenetic mechanisms

Abstract

Growing evidence suggests that epigenetic changes through various parental environmental factors alter the phenotypes of descendants in various organisms. Environmental factors, including exposure to chemicals, stress and abnormal nutrition, affect the epigenome in parental germ cells by different epigenetic mechanisms, such as DNA methylation, histone modification as well as small RNAs via metabolites. Some current remaining questions are the causal relationship between environment-induced epigenetic changes in germ cells and altered phenotypes of descendants, and the molecular basis of how the abnormal epigenetic changes escape reprogramming in germ cells. In this review, we introduce representative examples of intergenerational and transgenerational inheritance of phenotypic changes through parental environmental factors and the accompanied epigenetic and metabolic changes, with a focus on animal species. We also discuss the molecular mechanisms of epigenomic inheritance and their possible biological significance.

Prioritization of Appearance over Health and Temperament Is Detrimental to the Welfare of Purebred Dogs and Cats

“…In other species, effects of earlylife environmental factors on later health can be mediated by epigenetic modifications to DNA that 'program' the expression of genes [89]. Although the sequence of the DNA is not changed, some of these epigenetic changes appear to heritable [90,91]. If this type of inheritance is confirmed in dogs and cats, the significance of providing good environments for young puppies and kittens as well as their parents could extend beyond the individuals to future generations.…”

Multi-omics data analysis supporting inheritance of acquired traits in humans

“…Accumulating evidence supports presence of nongenetic germline inheritance of induced traits in animals including mammals (Anastasiadi et al ., 2021; Beil et al ., 2023; Cavalli and Heard, 2019; Dali et al, 2023; Fitz-James and Cavalli, 2022; Perez and Lehner, 2019; Santilli and Boskovic, 2023; Tando and Matsui, 2023). This unconventional, non-DNA sequence-based transmission of phenotypic information across organismal generations, often referred to as transgenerational epigenetic inheritance (TEI), is considered to be mediated by factors such as DNA methylation, histone post-translational modifications, and RNA (Cavalli and Heard, 2019; Perez and Lehner, 2019; Anastasiadi et al ., 2021; Santilli and Boskovic, 2023; Takahashi et al ., 2023).…”

“…Besides TEI, intergenerational inheritance, that may not necessarily implicate germline transmission but nonetheless share features with the former, is also considered relevant in nongenetic inheritance. Overall, germline mediated epigenetic inheritance contradicts multiple fundamental concepts in biology including neo-Darwinian principle that limits the source of heredity exclusively to DNA sequence, Weismann barrier that prohibits soma to germline transfer of hereditary information, and developmental reprogramming that inhibits germline inheritance of epigenetic signals, and hence has intriguing implications for ecology, evolution, and health and disease (Cavalli and Environmentally induced maternal TEI, first described as a consequence of exposure of gestating female rats to an endocrine disrupting compound (Anway et al, 2005), has been shown in invertebrates and vertebrates alike, with triggers including toxicants and pollutants, dietary factors, and stress, besides others (Bohacek and Mansuy, 2017; Cavalli and Heard, 2019; Dali et al, 2023;Perez and Lehner, 2019; Fitz-James and Cavalli, 2022; Santilli and Boskovic, 2023; Tando and Matsui, 2023). However, difficulties in eliminating confounders like genetic differences especially in rat models lacking inbred stocks, maternal contribution, and in utero and postnatal effects in female exposure TEI models remain a concern (Bohacek and Mansuy, 2017;Cavalli and Heard, 2019).…”

“…Given this, male exposure and patrilineal models of inheritance involving founders with similar genetic background are considered relatively less confounding and hence the focus of recent investigations (Bohacek and Mansuy, 2017; Cavalli and Heard, 2019; Perez and Lehner, 2019). With environmentally induced paternal TEI first described in the fruit fly Drosophila using a neuroactive compound as the trigger in an isogenic fly line (Sharma and Singh, 2009), male exposure and male line mediated inheritance, inter- or trans-generational, has been shown in various species including mammals (Beil et al, 2023; Bohacek and Mansuy, 2017; Perez and Lehner, 2019; Fitz-James and Cavalli, 2022; Santilli and Boskovic, 2023; Tando and Matsui, 2023).…”

“…Environmentally induced maternal TEI, first described as a consequence of exposure of gestating female rats to an endocrine disrupting compound (Anway et al ., 2005), has been shown in invertebrates and vertebrates alike, with triggers including toxicants and pollutants, dietary factors, and stress, besides others (Bohacek and Mansuy, 2017; Cavalli and Heard, 2019; Dali et al, 2023; Perez and Lehner, 2019; Fitz-James and Cavalli, 2022; Santilli and Boskovic, 2023; Tando and Matsui, 2023). However, difficulties in eliminating confounders like genetic differences especially in rat models lacking inbred stocks, maternal contribution, and in utero and postnatal effects in female exposure TEI models remain a concern (Bohacek and Mansuy, 2017; Cavalli and Heard, 2019).…”