Modern technologies in the study of clinical heterogeneity and molecular subtypes of pre-eclampsia

This review focuses on modern technologies for investigating the pathogenic mechanisms of pre-eclampsia—a serious pregnancy complication that remains one of the leading causes of maternal and perinatal morbidity and mortality. Over the past decades, global scientific research has made significant advances in the study of pre-eclampsia, particularly its pathogenesis. Key roles have been identified for oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and secondary endothelial dysfunction, as well as for angiogenic and anti-angiogenic factors, activation of the complement cascade, and the hemostatic system. Nevertheless, highly effective methods for predicting, preventing, and treating this pregnancy complication have not yet been developed. A possible reason, which has been receiving increasing attention in recent years, may lie in the existence of multiple subtypes of pre-eclampsia that differ in molecular mechanisms of development, severity and extent of lesions, as well as maternal and perinatal outcomes. In this regard, there is a need for deeper and more comprehensive exploration of the pathophysiology of pre-eclampsia using innovative high-throughput technologies that allow for simultaneous assessment of the full spectrum of systemic changes associated with pre-eclampsia. Such requirements are met by Big Data technologies utilizing various omics platforms, including epigenomics, genomics, transcriptomics, proteomics, metabolomics, and others. This article reviews the findings of published studies investigating the transcriptome, proteome, and peptidome of biological fluids and placental tissue in pregnant women with different clinical phenotypes of pre-eclampsia. When considered alongside clinical and anamnestic data and histological variants of placental changes, these findings allow for the identification of molecular subtypes of pre-eclampsia. The review demonstrates that the clinical heterogeneity of pre-eclampsia is driven by the wide variability of underlying molecular and genetic mechanisms. Special attention is given to studies employing a multi-omics approach. The analysis of publications in this review underscores the importance of accounting for identified molecular subtypes in the development of personalized management strategies for pregnant women, as well as individualized approaches to prediction and prevention of pre-eclampsia and evidence-based pregnancy prolongation or early delivery. The article also presents promising directions for further research into the pathophysiology of pre-eclampsia using omics technologies, the accumulation and analysis of which may contribute to improving the diagnosis, prevention, and treatment of this pregnancy complication through the development of potential biomarkers and molecular targets.