Small RNAs in the pathogenesis of preeclampsia

• Published in: Placenta (Eastbourne) 2024-11, Vol.157, p.21-27
• Main Authors: Cooke, William R., Jones, Gabriel Davis, Redman, Christopher WG, Vatish, Manu
• Format: Article
• Language: English
• Subjects: Female; Humans; Micro RNA; MicroRNAs - genetics; MicroRNAs - metabolism; Piwi-interacting RNA; Placenta - metabolism; Pre-Eclampsia - etiology; Pre-Eclampsia - genetics; Pre-Eclampsia - metabolism; Preeclampsia; Pregnancy; Small nucleolar RNA; Small RNA; Transfer RNA
• ISSN: 0143-4004; 1532-3102; 1532-3102
• DOI: 10.1016/j.placenta.2024.06.009

Preeclampsia is a major contributor to maternal and fetal morbidity and mortality. The disorder can be classified into early- and late-onset subtypes, both of which evolve in two stages. The first stage comprises the development of pre-clinical, utero-placental malperfusion. Early and late utero-placental malperfusion have different causes and time courses. Early-onset preeclampsia (20 % of cases) is driven by dysfunctional placentation in the first half of pregnancy. In late-onset preeclampsia (80 % of cases), malperfusion is a consequence of placental compression within the confines of a limited uterine cavity. In both subtypes, the malperfused placenta releases stress signals into the maternal circulation. These stress signals trigger onset of the clinical syndrome (the second stage). Small RNA molecules, which are implicated in cellular stress responses in general, may be involved at different stages. Micro RNAs contribute to abnormal trophoblast invasion, immune dysregulation, angiogenic imbalance, and syncytiotrophoblast-derived extracellular vesicle signalling in preeclampsia. Transfer RNA fragments are placental signals known to be specifically involved in cell stress responses. Disorder-specific differences in small nucleolar RNAs and piwi-interacting RNAs have also been reported. Here, we summarise key small RNA advances in preeclampsia pathogenesis. We propose that existing small RNA classifications are unhelpful and that non-biased assessment of RNA expression, incorporation of non-annotated molecules and consideration of chemical modifications to RNAs may be important in elucidating preeclampsia pathogenesis. •Small RNAs are implicated at multiple stages of preeclampsia pathogenesis.•Micro RNAs are the most studied; novel data indicate other species are important.•Existing small RNA classifications can be unhelpful.•We promote non-biased small RNA assessment, including non-annotated molecules.