DNA methylation landscape in pregnancy-induced hypertension: progress and challenges

Abstract

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

Keywords: DNA methylation; Diagnosis and Treatment; Prediction; Pregnancy-induced hypertension.

Fig. 1

The outline of this review

Fig. 2

Possible factors affecting the results of global DNA methylation levels in PIH placenta

Fig. 3

The occurrence of PIH is associated with differential DNA methylation of placental genes. This figure illustrates the genes in the placenta that contribute to PIH due to variations in DNA methylation. These genes include imprinted genes, tumor suppressor genes, placental classical signaling pathways, placental microRNAs, and several other protein genes. Abbreviation: hyper, hypermethylation; hypo, hypomethylation; + , promote; -, inhibit; TFPI2, tissue factor pathway inhibitor 2; VHL, von Hippel Lindau tumor suppressor; RARRES1, retinoic acid receptor responder 1; TGF, transforming growth factor; DLL1, Delta-like 1; BCL-2, B-cell CLL/lymphoma 2; FABP4, fatty acid binding protein 4; ROS, reactive oxygen species; Bcl-xl, B-cell lymphoma-extra large; YAP1, Yes-associated protein 1; FOXO3, Forkhead-box O3; IGFBP5, insulin-like growth factor-binding protein 5; IGF, insulin-like growth factor; PAX3, Paired Box 3; YWHAQ, Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide; ERO1α, endoplasmic reticulum oxidase 1α; SERPINA3, serpin peptidase inhibitor clade A member 3; CMIP, C-Maf inducing protein; CTGF, connective tissue growth factor