Recent progress towards understanding the role of DNA methylation in human placental development

Abstract

Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses.

The role of DNA methylation in human trophoblast differentiation

“…It is clear that DNA methylation differences exist between primary human trophoblast populations [21]. These methylation changes are known to influence expression of genes involved in regulating; cell proliferation, the immune system, and cell invasion [14,15,22].…”

Placental mesenchymal dysplasia with a good outcome: A case report

“…In a case of an adverse maternal environment, a male infant placenta responds with a continuous growth regardless of its survival vulnerability, whereas a female infant placenta responds with multiple adaptations leading to increased survival even with a decrease in growth compromising oxygen and nutrition supply . Furthermore, genomic imprinting associated with DNA methylation not only in the fetus but also in the placenta is recently discussed related to PMD pathogenesis . Some reports showed there are sex‐related differences in the sensitivity to DNA methylation, and also fetal sex differences in placental DNA methylation as well …”

“…Furthermore, genomic imprinting associated with DNA methylation not only in the fetus but also in the placenta is recently discussed related to PMD pathogenesis . Some reports showed there are sex‐related differences in the sensitivity to DNA methylation, and also fetal sex differences in placental DNA methylation as well …”

Placental adaptations to micronutrient dysregulation in the programming of chronic disease

“…Epigenetics is a term used to describe a range of chemical and structural modifications that regulate genome accessibility and therefore gene transcription without causing changes to the DNA sequence. 49 Epigenetic mechanisms regulate which genes are expressed within each cell as well as when they are expressed. Dietary and environmental factors most commonly influence gene expression through a number of epigenetic pathways.…”