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Review
. 2019 Dec 3;8(12):1559.
doi: 10.3390/cells8121559.

Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

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Review

Transgenerational Inheritance of Environmentally Induced Epigenetic Alterations during Mammalian Development

Louis Legoff et al. Cells. .

Abstract

Genetic studies traditionally focus on DNA as the molecule that passes information on from parents to their offspring. Changes in the DNA code alter heritable information and can more or less severely affect the progeny's phenotype. While the idea that information can be inherited between generations independently of the DNA's nucleotide sequence is not new, the outcome of recent studies provides a mechanistic foundation for the concept. In this review, we attempt to summarize our current knowledge about the transgenerational inheritance of environmentally induced epigenetic changes. We focus primarily on studies using mice but refer to other species to illustrate salient points. Some studies support the notion that there is a somatic component within the phenomenon of epigenetic inheritance. However, here, we will mostly focus on gamete-based processes and the primary molecular mechanisms that are thought to contribute to epigenetic inheritance: DNA methylation, histone modifications, and non-coding RNAs. Most of the rodent studies published in the literature suggest that transgenerational epigenetic inheritance through gametes can be modulated by environmental factors. Modification and redistribution of chromatin proteins in gametes is one of the major routes for transmitting epigenetic information from parents to the offspring. Our recent studies provide additional specific cues for this concept and help better understand environmental exposure influences fitness and fidelity in the germline. In summary, environmental cues can induce parental alterations and affect the phenotypes of offspring through gametic epigenetic inheritance. Consequently, epigenetic factors and their heritability should be considered during disease risk assessment.

Keywords: environmental factors; epigenetics; genome reprograming; histone modifications; transgenerational inheritance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The transgenerational inheritance and histone modifications in the mouse. In the zygote, the paternal genome appears to be generally depleted of H3K4me3. Strong paternal H3K4me3 peaks reappear during the late two-cell stage. However, the levels of H3K4me3 become comparable between maternal and paternal genomes only after implantation. At the late two-cell stage, non-canonical H3K4me3 peaks (broad and low-intensity peaks) are replaced by canonical H3K4me3 (narrow and strong-intensity peaks). In early-stage (pre-implantation), H3K27me3 marks are enriched at distal promoters far from transcription start sites (TSS) in paternal and maternal genomes. At later stages (E5.5), they are generally enriched at TSS. Primordial germ cells move into the genital ridges at E11.5 and differentiate into spermatocytes or oocytes. Both canonical and noncanonical H3K27me3 are found in developing and mature oocytes. During spermatogenesis, histones are replaced by protamines, whereby only ~10% of histones are preserved. The environmental exposure to toxicants could promote changes in germline cells at any developmental stage, with more dramatic effects being observed during embryonic germ cell reprogramming. The exposed germline cells produce spermatozoa with altered epigenetic features. Finally, these epigenetic changes could be preserved up to several generations via histone retention mechanism. Figure adapted from [65,145,181].

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