Administration of i-PRF Improved Repair of Thin Endometrium via Mitochondrial Transfer

Background Thin endometrium has been widely accepted as a key factor responsible for uterine infertility and impaired outcomes of assisted reproductive therapy. Platelet derivatives showed promising therapeutic outcomes in promoting tissue repair. Here, we investigated the role of injectable platelet-rich fibrin (i-PRF) in treating thin endometrium (TE) in a rat model by injecting 95% ethanol into the uterine cavity. Methods i-PRF was prepared and its biological properties were tested. Animals were randomly divided into two main groups, which were further subdivided into four subgroups according to the experimental interventions applied to the uterine horns: control, Model, Ethanol + NS, and Ethanol + i-PRF injection groups. Morphological alterations in the uterine wall were observed by H&E and immunohistochemical staining. Endometrial receptivity was evaluated by detecting the expression of receptivity markers and counting the number of embryo implantations. Results We found that the secretion of VEGF-A, TGF-β1, and PDGF-AB growth factors in i-PRF can last for nearly 15 days, with a peak in the first 7 days. Intrauterine administration of i-PRF markedly increased endometrial thickness and gland numbers. Meanwhile, the number of embryo implantations was significantly increased in thin endometrium treated with i-PRF, along with enhanced expression of LIF and VEGF-A. Co-culture of i-PRF-derived platelets remarkably promoted the proliferation of ESCs, which was also observed in i-PRF-treated uteri. Notably, we observed mitochondria translocation from platelets to endometrial stromal cells (ESCs), which showed high proliferating potential. Blockage of respiratory function before transfer resulted in a diminished effect of mitochondria in stimulating the reparative capacity of ESCs. Conclusions Our experiment revealed the therapeutic potential of i-PRF in treating thin endometrium and the role of mitochondrial transfer from platelet derivatives in promoting endometrial regeneration.