Identification of syncytiotrophoblast-derived cf-RNA OPA1 to predict the occurrence of preeclampsia

Background: Pre-eclampsia (PE) poses a significant threat to mothers and infants worldwide. Studies indicate that taking low-dose aspirin before the 16th week of pregnancy may prevent approximately 70 % of PE cases, highlighting the importance of predicting PE. Cell-free RNA (cf-RNA) exhibits significant changes in the maternal peripheral blood during early pregnancy, making cf-RNA analysis a promising and less invasive method for predicting PE.

Methods: The two datasets, GSE192902 and GSE149440, were analyzed to identify differentially expressed cf-RNAs, followed by the calculation of their AUC values Subsequently, these cf-RNAs were validated using placental tissues, as well as late- and early-stage plasma samples collected from both healthy individuals and patients with PE. Furthermore, we performed tissue localization and functional analyses on the ultimate candidate gene.

Results: Mitochondrial Dynamin-Like GTPase (OPA1) emerged as the molecule with the most consistent and statistically significant alterations in placental tissues and serum samples from patients with PE across various gestational weeks. Notably, the combination of OPA1 levels and mean arterial pressure (MAP) yielded an AUC of 0.825 (95 % CI: 0.759-0.879) for predicting PE. Additionally, we verified that OPA1 is predominantly expressed in placental syncytiotrophoblast (STB) cells, and its downregulation negatively impacts STB mitochondrial function, angiogenic potential, and cell proliferation.

Conclusions: OPA1 holds the potential to emerge as a novel cf-RNA for predicting PE.