Mechanisms of transgenerational epigenetic inheritance: lessons from animal model organisms

Santilli, Flavio; Bošković, Ana

doi:10.1016/j.gde.2023.102024

Cited by 13 publications

(20 citation statements)

References 54 publications

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“…Environmental effects on the mother are widely known to contribute to intergenerational inheritance and the underlying mechanisms have been extensively studied. For example, maternal obesity and hormonal imbalance can predispose the offspring to type 2 diabetes and obesity; or maternal zinc deficiency can impact offspring development reducing birth weight, altering the offspring's lipid metabolism or increasing their resistance to insulin; maternal gestational exposure to cadmium can lead to hormonal changes in the F2; and maternal stress can increase the levels of stress hormones in their grandchildren (Lawless et al., 2023; Lecoutre et al., 2021; Mbiydzenyuy et al., 2022; Şanlı & Kabaran, 2019; Santilli & Boskovic, 2023; Sanusi et al., 2021; Stäubli & Peters, 2021).…”

Section: Introductionmentioning

confidence: 99%

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Jimenez‐Gonzalez,

Ansaloni,

Nebendahl

et al. 2024

Molecular Ecology

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Dietary restriction in the form of fasting is a putative key to a healthier and longer life, but these benefits may come at a trade‐off with reproductive fitness and may affect the following generation(s). The potential inter‐ and transgenerational effects of long‐term fasting and starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split‐egg clutch design to explore the male‐specific effects of fasting/starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected increased larval growth rate in F1 offspring from starved males and more malformed embryos at 24 h post‐fertilisation in F2 offspring produced by F1 offspring from starved males. Comparing the transcriptomes of F1 embryos sired by starved and fed fathers revealed robust and reproducible increased expression of muscle composition genes but lower expression of lipid metabolism and lysosome genes in embryos from starved fathers. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal effects on extra‐embryonic tissues which are loaded with maternal factors. We compared the embryo transcriptomes to published adult transcriptome datasets and found comparable repressive effects of starvation on metabolism‐associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring's nutritional state, which was defined by the mother.

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Section: Introductionmentioning

confidence: 99%

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Jimenez‐Gonzalez,

Ansaloni,

Nebendahl

et al. 2024

Molecular Ecology

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“…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 sequencebased 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.…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Epidemiological and ancestral exposure studies also suggest potential presence of epigenetic inheritance in humans (Hart and Tadros, 2019; Senaldi and Smith-Raska, 2020; Vågerö et al ., 2022; Dachew et al ., 2023; Kaufman et al ., 2023; Niu et al ., 2023; Santilli and Boskovic, 2023). Additionally, considering the obvious difficulties in conducting human cross-generational studies (Senaldi and Smith-Raska, 2020; Santilli and Boskovic, 2023), molecular support for paternal germline inheritance of environmental effects in humans has recently been found in terms of father’s smoking showing association with offspring blood DNA methylation (Kitaba et al ., 2023). Nevertheless, with integrative genome scale data analysis (Molaro et al ., 2011; Cavalli and Heard, 2019; Sharma, 2020; Niu et al ., 2023) and leveraging animal evidence (Perez and Lehner, 2019; Fitz-James and Cavalli, 2022; Bhalla and Sharma, 2023) considered as valuable approaches in epigenetic inheritance, it remains unexplored if applying these approaches could provide further insights into possible existence of nongenetic germline inheritance in humans.…”

Section: Introductionmentioning

confidence: 99%

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

Sharma

2023

Preprint

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Emerging evidence increasingly supports germline mediated non-DNA sequence-based inheritance of environmentally induced traits in animals including mammalian models. Epidemiological and ancestral exposure studies also suggest possible presence of epigenetic inheritance in humans. Notably, cross-species conservation of phenotypic responses in non-genetic inheritance has recently been shown in transcriptomic analysis of Drosophila and rodent models. Here, an unbiased analysis of available human and animal model multi-omics data is presented that supports inheritance of induced traits in humans. First, in an analysis feasibility survey, physical exercise was identified as the lone environmental factor that is known to affect conserved physiological pathways and to induce inheritance in animal models, and at the same time, the effects of which on human cohort sperm DNA methylome, and human cohort, rat, mouse and Drosophila coding and/or non-coding somatic transcriptome have also been multiply described. The hypothesis was thus tested that exercise induced human sperm DNA methylation changes can specifically explain exercise induced human and animal model somatic transcriptome changes. For controlling the analysis, bariatric surgery, identified as the lone environmental factor for which human cohort sperm DNA methylome and somatic transcriptome datasets are multiply available, was used. Remarkably, the hypothesis was supported in all pre-specified tests, involving gene set overlap, gene ontology enrichment, promotor methylation and gene regulation directionalities, and coding and non-coding transcriptome interactions. The results presented support germline encoding of acquired traits in humans, thus suggesting existence of epigenetic inheritance in our species.

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HDAC3 inhibition protects against peripheral and central alterations in an animal model of obesity

Machado,

Boeira,

Bortolotto

et al. 2023

Pharmacol. Rep

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Mechanisms of transgenerational epigenetic inheritance: lessons from animal model organisms

Cited by 13 publications

References 54 publications

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness

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

HDAC3 inhibition protects against peripheral and central alterations in an animal model of obesity

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