Brief intro:
- Author: Chao Ding, Fukang Liu, Huayue Shi, Jing Zuo, Lei Bi, Longgang Shao, Yanqiu Pan
- Journal: PeerJ
- Doi: https://www.doi.org/10.7717/peerj.19568
- Publication Date: 2025 Jun 24
Abstract
Background: Recurrent spontaneous abortion (RSA) affects 1–5% of pregnant women; however, the mechanisms underlying this condition remain unknown. Dysangiogenesis in the placenta is an essential factor in the pathogenesis of RSA. Studies have verified that microRNAs (miRNAs) are vital for RSA; however, their mechanism of action in regulating angiogenesis remains unclear. Therefore, we explored the contribution of key miRNAs that regulate angiogenesis in RSA.
Methods: The abortion mouse model was constructed by intraperitoneal injection of beta2-Glycoprotein I (β2-GPI). The abnormal expression of miRNAs in the placenta of the abortion mice was screened using miRNA-seq. Based on miRNA databases, miR-381-3p, which is highly expressed in abortion mice, may bind to vascular endothelial growth factor A (VEGFA). Subsequently, we investigated the effects of the miR-381-3p/VEGFA axis on the angiogenesis of vascular endothelial cells using real-time quantitative polymerase chain reaction, Transwell, wound healing, tube formation, western blotting, and dual-luciferase reporter system. Furthermore, an in vivo experiment was used to confirm miR-381-3p knockdown contribution in the abortion mouse model.
Results: miR-381-3p overexpression inhibited the migration and angiogenesis of C166 cells (a mouse vascular endothelial cell line), whereas miR-381-3p knockdown had the opposite effect. The dual-luciferase reporter system revealed that miR-381-3p bound to the VEGFA 3′ UTR, and VEGFA knockdown counteracted the beneficial effect of the miR-381-3p inhibitor on angiogenesis. An in vivo study demonstrated that miR-381-3p knockdown may reduce inflammation and damage to the placenta and fetus during abortion by activating the VEGFA/nuclear factor kappa B (NF-κB) pathway.
Conclusion: miR-381-3p may cause insufficient placental blood flow by inhibiting the VEGFA pathway and can be used as a potential therapeutic target for RSA.
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