Trophoblast invasion dynamics improve through protein-mediated enhancement of uterine vascular remodelling pathways

Background: In early pregnancy, trophoblast invasion and uterine vascular remodelling must be tightly regulated to ensure maternal-foetal circulation. Inhibition of these processes causes preeclampsia, foetal development retardation, and recurrent pregnancy loss. It is unclear whether molecular regulators control trophoblast invasiveness and uterine vascular adaption, despite much investigation. Methods: Here, a Protein-Mediated Vascular Remodelling Enhancement (PM-VRE) technique is proposed to examine trophoblast invasion mediated by particular regulatory proteins by increasing uterine vascular remodelling. Protein expression profiling and pathway interaction analysis comprise PM-VRE. Results: Experiments show protein signalling drives endothelial transformation, artery remodelling, and trophoblast migration, with upregulated angiogenic and matrix pathways enabling vascular adaptation. It achieves higher trophoblast invasion depths (∼195-210 µm), enhanced endothelial responsiveness (up to 95%), increased ECM remodelling activity (∼75-80), greater vascular resistance reduction (∼78%), and improved placental perfusion stability (up to 90). Conclusion: PM-VRE provides an effective framework for identifying molecular regulators of trophoblast invasion and uterine vascular remodeling, offering insights into mechanisms underlying placental development and pregnancy disorders associated with impaired placentation.