MELTF Might Regulate Ferroptosis, Pyroptosis, and Autophagy in Platelet-Rich Plasma-Mediated Endometrial Epithelium Regeneration

The endometrial basal layer is essential for endometrial regeneration, whose disruption leads to thin endometrium or intrauterine adhesion (IUA) with an unsatisfactory prognosis. Emerging data indicate that platelet-rich plasma (PRP) can promote endometrial proliferation, but the mechanism by which PRP regulates endometrial regeneration remains unclear. Herein, we investigated the therapeutic effects and possible mechanisms of PRP on endometrial regeneration. IUA animal model was generated by sham, mechanically damaging endometrium with or without PRP for 10 days. The uterine section in the model group showed degenerative changes with a narrow endometrial lumen, atrophic columnar epithelium, decreased number of endometrial glands, decreased endometrial thickness, and increased collagen deposition. The above disruption could be ameliorated by the PRP. Transcriptome sequencing analysis displayed that the retinol metabolism pathway and extracellular matrix (ECM) receptor interaction pathway were up-regulated and enriched in differential expression genes (DEGs). Melanotransferrin (MELTF) was the key up-regulated gene in PRP-induced endometrial regeneration, which was verified in vivo and in vitro. Ferroptosis, autophagy, and pyroptosis were down-regulated in PRP-treated Ishikawa cells. Conclusively, PRP promotes endometrium regeneration by up-regulating the retinol metabolism and ECM receptor interaction pathway with MELTF. Meanwhile, PRP could also inhibit endometrial epithelial cell death by regulating ferroptosis, autophagy, and pyroptosis.