A Single-Cell Transcriptomic Map Reveals Platelet-Rich Plasma-Induced Endometrial Microenvironment Remodeling in Recurrent Implantation Failure

Intrauterine infusion of platelet-rich plasma shows clinical promise as a regenerative therapy for patients with repeated implantation failure, yet the precise cellular and molecular mechanisms governing its in vivo effects on the human endometrium remain poorly understood. To elucidate these mechanisms at high resolution, we performed single-cell RNA sequencing on paired endometrial biopsies collected from patients during the proliferative phase, both before and shortly after intrauterine platelet-rich plasma infusion. Our analysis reveals that platelet-rich plasma acts as a potent modulator of the endometrial microenvironment by inducing extensive transcriptional reprogramming within resident cell populations. Alongside the direct stimulatory effects of PRP on various cell lineages, stromal cells emerged as key mediators contributing to this regenerative response, suppressing developmental plasticity pathways while concomitantly upregulating functions crucial for tissue regeneration, including cytoskeletal remodeling, pro-angiogenic signaling, and immune modulation. These reprogrammed stromal cells are predicted to serve as functional hubs, potentially driving enhanced paracrine networks that support robust angiogenesis through endothelial cell expansion and promote a growth-favorable epithelial phenotype via secreted growth factors. Notably, platelet-rich plasma infusion also induced a marked expansion and activation of specific tissue-resident natural killer cell subsets, indicating a recalibration of the local immune landscape. This study highlights that platelet-rich plasma orchestrates a multifaceted regenerative program where direct cellular stimulation converges with reprogrammed stromal-driven paracrine signaling to facilitate vascularization, epithelial growth, and immunological recalibration in the endometrium.