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. 2019 Oct 23;16(3):465-474.
doi: 10.21451/1984-3143-AR2019-0062.

DNA methylation, environmental exposures and early embryo development

Mélanie Breton-Larrivée  1 , Elizabeth Elder  1 , Serge McGraw  1   2
Affiliations

DNA methylation, environmental exposures and early embryo development

Mélanie Breton-Larrivée et al. Anim Reprod. .

Abstract

The first crucial step in the developmental program occurs during pre-implantation, the time after the oocyte has been fertilized and before the embryo implants in the uterus. This period represents a vulnerable window as the epigenome undergoes dynamic changes in DNA methylation profiles. Alterations in the early embryonic reprogramming wave can impair DNA methylation patterns and induce permanent changes to the developmental program, leading to the onset of adverse health outcomes in offspring. Although there is an increasing body of evidence indicating that harmful exposures during pre-implantation embryo development can trigger lasting epigenetic alterations in offspring, the mechanisms are still not fully understood. Since physiological or pathological changes in DNA methylation can occur as a response to environmental cues, proper environmental milieu plays a critical role in the success of embryonic development. In this review, we depict the mechanisms behind the embryonic epigenetic reprogramming of DNA methylation and highlight how maternal environmental stressors (e.g., alcohol, heat stress, nutrient availability) during pre-implantation and assisted reproductive technology procedures affect development and DNA methylation marks.

Keywords: DNA methylation; developmental programming; epigenetics; pre-implantation embryos; prenatal exposures.

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Conflict of interest statement

Conflict of interest Authors declare that they have no conflict of interest

Figures

Figure 1
Figure 1. Global DNA demethylation and remethylation during the epigenetic reprogramming of early embryogenesis in mice. Soon after fertilization, the zygotic paternal and maternal pronuclei undergo global demethylation during the pre-implantation stages, except for gDMRs which are maintained via DNMT1 activity. The paternal genome (blue) is initially actively demethylated by the TET3 enzyme followed by passive demethylation, whereas the maternal genome (red) demethylation is solely passive due to DNMT1 inactivity, hence the sharper demethylation slope for the paternal curve. After implantation, the blastocyst acquires de novo methylation patterns catalyzed by DNMT3A and DNMT3B to establish the embryonic and placental programs imperative for development initiation.
See this image and copyright information in PMC

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