The Role of miR-181a in Preeclampsia: Modulating TrophoblastProliferation and Migration via Estrogen Receptor 1

Introduction: Preeclampsia is a pregnancy-specific hypertensive disorder associated with abnormal trophoblast function. MicroRNA-181a (miR-181a) has been implicated in placental development, but its role in trophoblast behavior and its interaction with estrogen receptor 1 (ER1) remain unclear. This study aimed to investigate the functional role of miR-181a in trophoblast proliferation and migration and to determine whether ER1 mediates these effects in the context of preeclampsia. Methods: Methods: Placental tissues were collected from 30 PE patients and 26 healthy controls. Expression levels of miR-181a and ESR1 were quantified by qRT-PCR. The effects of miR-181a on trophoblast viability, proliferation, and migration were assessed using CCK-8 and Transwell assays. The direct targeting of ESR1 by miR-181a was validated via dual-luciferase reporter assays. Results: Results: miR-181a was significantly upregulated in PE placental tissues compared to controls (P < 0.001), whereas ESR1 expression was markedly downregulated (P < 0.001). A significant negative correlation between miR-181a and ESR1 levels was observed (P < 0.001). Functional assays revealed that miR-181a overexpression (OE) promoted trophoblast proliferation and migration, whereas its inhibition exerted opposite effects. Luciferase reporter assays confirmed direct binding of miR-181a to the 3'-UTR of ESR1, leading to reduced ESR1 expression. Ectopic ESR1-OE reversed the effects of miR-181a on trophoblast viability and migration. Discussion: Our findings demonstrate that miR-181a negatively regulates trophoblast proliferation and migration, and that ER1 is a direct target of miR-181a. Downregulation of miR-181a restored trophoblast function, suggesting a potential therapeutic target for preeclampsia. These results align with prior studies linking miRNA dysregulation to placental insufficiency. However, this study is limited by its in vitro design, and future in vivo validation is warranted to confirm the clinical relevance of miR-181a-ER1 signaling in preeclampsia pathogenesis. Conclusion: miR-181a contributes to PE pathogenesis by negatively regulating ESR1, thereby impairing trophoblast proliferation and migration. These findings provide novel insights into the molecular mechanisms of PE and suggest miR-181a as a potential diagnostic or therapeutic target.