Hsa-miR-532-3p protects human decidual mesenchymal stem cells from oxidative stress in recurrent spontaneous abortion via targeting KEAP1

作者：Hong Zhou, Jiaxin Zhou, Shanshan Liu, Jing Niu, Jinghua Pan, Ruiman Li · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103508 · 被引用次数：6 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Preterm Birth and Chorioamnionitis

BACKGROUND: Human decidual mesenchymal stem cells (hDMSCs) play crucial roles in pregnancy. The decreased resistance of hDMSCs to oxidative stress is a key factor contributing to recurrent spontaneous abortion (RSA). miRNAs have essential functions in the proliferation and apoptosis of decidual tissues. However, the miRNAs involved in regulating oxidative stress in hDMSCs remain unclear. METHODS: Decidual tissues and hDMSCs were collected from patients with RSA and early pregnancy miscarriages. We assessed the antioxidant capacity of hDMSCs in both groups by detecting relevant indicators. Furthermore, differentially expressed miRNAs in hDMSCs were analyzed through miRNA sequencing. We evaluated the interaction between hsa-miR-532-3p and KEAP1 using a luciferase reporter assay. A mouse model of RSA was constructed for confirmation. Finally, we analyzed the correlations between serum hsa-miR-532-3p levels and the clinical features of pregnant women with RSA. RESULTS: miRNA sequencing revealed 44 miRNAs whose expression was downregulated and 9 miRNAs whose expression was upregulated in hDMSCs from the RSA group compared with those from the control group. The overexpression of hsa-miR-532-3p led to a significantly increased antioxidant capacity in hDMSCs. The knockdown or overexpression of hsa-miR-532-3p led to the upregulation or downregulation of KEAP1 expression, respectively. In a mouse model, the overexpression of hsa-miR-532-3p reduced embryo absorption rates in RSA mice, d...