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bioRxiv · 10.1101/2025.10.06.680827

Bioinformatic analysis of placental exomiRs targeting the brain in preeclampsia

Alarcon, M.·Aguayo, C.·Vatish, M.·Escudero, C.
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Abstract

BackgroundPreeclampsia is a hypertensive disorder of pregnancy associated with systemic endothelial dysfunction and, in severe cases, maternal neurological complications. Placenta-derived exosomal microRNAs (exomiRs) mediate inter-organ communication and may contribute to neurovascular injury, but their role in maternal brain dysregulation remains unclear. MethodsWe performed systems-level bioinformatic analyses of 12 differentially expressed exomiRs (6 from early-onset and 6 from late-onset preeclampsia) to assess their potential impact on brain homeostasis. Target interactomes were examined for functional enrichment, subcellular localization, and network complexity. ExomiR targets were integrated with cerebrospinal fluid (CSF) proteomic profiles from preeclamptic women with neurological symptoms. We further evaluated regulation of blood-brain barrier (BBB) components and mapped spatial expression of target proteins across brain regions and cell types relevant to neurovascular function. ResultsEarly-and late-onset preeclampsia exomiRs displayed distinct interactomes and biological signatures. Early-onset exomiRs were linked to RNA metabolism, oxidative stress, and endothelial stability, whereas late-onset exomiRs were enriched in nitrogen metabolism and vesicle-mediated transport. Integration with CSF proteomics revealed convergence on dysregulated proteins, including MAPK8, RTN4, and YWHA family members, involved in inflammation, neurodegeneration, and axonal inhibition. Several exomiRs targeted BBB-related proteins (CLDN2, TJP1, EFNA5), suggesting coordinated barrier disruption. Spatial mapping localized these targets to endothelial cells, astrocytes, interneurons, and pyramidal neurons, implicating altered synaptic and glial regulation. ConclusionsPreeclampsia-associated exomiRs may impair maternal brain homeostasis through coordinated regulation of neurovascular, inflammatory, and synaptic pathways. These findings identify candidate molecular mediators of preeclampsia-related neurovascular dysfunction and potential biomarkers for maternal brain injury.

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Alarcon, M., Aguayo, C., Vatish, M., Escudero, C.. 2025-10-09. Bioinformatic analysis of placental exomiRs targeting the brain in preeclampsia. https://doi.org/10.1101/2025.10.06.680827

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