LAUSR

Embryo implantation relies on complex mother-fetus interactions. Abnormal decidualization can cause various pregnancy complications such as placental abnormalities, preeclampsia, and fetal growth restriction. circRNAs play a key role in various cellular processes. This study focuses on the role of circ-Hdac4, a circRNA derived from the Hdac4 gene, in decidualization and placental function. Mouse models revealed a spatiotemporally regulated expression of circ-Hdac4 in the endometrium during early pregnancy, with enhanced expression surrounding implantation sites. In vitro and in vivo assays confirmed that circ-Hdac4 is crucial for stromal cell decidualization, as its knockdown resulted in reduced expression of decidualization markers and disrupted endometrial architecture. Furthermore, we found that circ-Hdac4 functions as a microRNA sponge for miR-30c, which negatively regulates RBPJ, a critical protein for decidual remodeling. Proteomic analysis revealed that RBPJ was downregulated upon circ-Hdac4 silencing, and we validated the direct interaction between miR-30c and RBPJ using luciferase reporter assays. A mouse preeclampsia model showed that downregulation of circ-Hdac4 during decidualization exacerbated preeclampsia-related phenotypes, including reduced fetal counts, weights, and placental weights. In addition, we observed decreased expression of circ-Hdac4 and RBPJ in the decidual surface of placental tissues from preeclampsia patients, further supporting our findings in the mouse model. Collectively, our study provides evidence that circ-Hdac4 regulates decidualization through the miR-30c-RBPJ axis and that its abnormal expression during decidualization contributes to placental dysfunction in preeclampsia. This research offers novel insights into the molecular mechanisms underlying pregnancy complications and potential therapeutic targets for their prevention and treatment. 1. circ-Hdac4 can regulate endometrial decidualization by targeting Mir-30c-RBPJ axis in early pregnancy mice 2. circ-Hdac4/miR-30c/RBPJ axis regulating decidualization through miRNA sponging, 3. Reduced circ-Hdac4 and RBPJ expression in human preeclampsia decidua correlates with placental dysfunction