Umbilical cord-derived exosomal miR-548 is involved in driving preeclampsia pathogenesis by Inhibiting trophoblast cells invasion.

BACKGROUND

Preeclampsia (PE) is a severe pregnancy-related disorder characterized by hypertension and end-organ manifestation, and remains a leading cause of perinatal maternal and fetal mortality and morbidity in developing countries. The pathogenesis of PE involves reduced uteroplacental blood flow and impaired trophoblast invasion; however, the role of exosomes in these processes is not fully understood.

METHODS

This study employed Transwell assay, wound healing assay, and CCK-8 assays to evaluate the effects of umbilical cord exosomes derived from women with PE (PE-exosomes) on trophoblast function. Additionally, miRNA sequencing, in vitro transfection, western blotting, RT-PCR amd FISH assays were used to investigate the involvement of the microRNA-548 (miR-548)/Ras homolog family member A (RhoA) axis. Statistical analysis was performed using t-tests, with a significance threshold of P  <  0.01.

RESULTS

Expression levels of miR-548 were significantly elevated in PE-exosomes. Both treatment with PE-exosomes and the overexpression of miR-548 inhibited trophoblast invasion and proliferation. These effects were reversed by RhoA overexpression. Together, these findings suggest that PE-exosomes suppress trophoblast invasion via the miR-548/RhoA axis. In pregnant women with PE, high miR-548 expression levels were observed, and were positively correlated with blood pressure and proteinuria.

CONCLUSIONS

Elevated miR-548 levels may contribute to the development of PE, suggesting that miR-548 could serve as a novel diagnostic or therapeutic target for this condition.