Elevated Hsa-miR-335-5p impairs trophoblast function and fetal growth in preeclampsia.

BACKGROUND

Preeclampsia (PE) is a pregnancy complication associated with abnormal placental development and fetal growth restriction. Despite progress in understanding PE, the molecular mechanisms underlying its pathogenesis remain poorly defined. Exosomal miRNAs, particularly hsa-miR-335-5p, have been implicated in the regulation of placental function, but their exact role in PE requires further investigation.

METHODS

We utilized advanced microfluidic chip technology to isolate and sequence serum exosomal miRNAs from PE patients and healthy controls. Functional assays were conducted to assess the effects of hsa-miR-335-5p overexpression on the proliferation, invasion, and apoptosis of trophoblast cells, especially under hypoxic conditions that replicate the placental microenvironment in PE. In vivo studies using a rat model were performed to examine the effects of elevated hsa-miR-335-5p on placental morphology and fetal growth. Mechanistic analysis was carried out to identify the target genes of hsa-miR-335-5p.

RESULTS

Our analysis revealed a significant upregulation of hsa-miR-335-5p in the serum exosomes of PE patients compared to controls. Overexpression of hsa-miR-335-5p in trophoblast cells resulted in inhibited proliferation, decreased invasion, and increased apoptosis, particularly under hypoxic conditions. In vivo, rats with elevated hsa-miR-335-5p showed disrupted placental structure and fetal growth restriction. The mechanistic analysis identified MEF2D as a direct target of hsa-miR-335-5p, which plays a critical role in regulating trophoblast development and function.

CONCLUSION

This study establishes hsa-miR-335-5p as a key regulator in the pathogenesis of PE by targeting MEF2D and disrupting trophoblast function. These findings suggest that hsa-miR-335-5p could serve as a potential biomarker and therapeutic target for PE, offering new strategies for the diagnosis and treatment of this pregnancy complication.