Mao Yanhong, Wang Mei, Xiong Yao, Wen Xue, Zhang Ming, Ma Ling, Zhang Yuanzhen
Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, NO. 169, East Lake Road, Wuchang District, Wuhan City, 430071, Hubei Province, China.
Reprod Sci. 2023 May;30(5):1506-1520. doi: 10.1007/s43032-022-01101-y. Epub 2022 Oct 27.
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.
子宫内膜基底层对于子宫内膜再生至关重要，其破坏会导致子宫内膜变薄或宫腔粘连（IUA），预后不佳。新出现的数据表明，富血小板血浆（PRP）可促进子宫内膜增殖，但PRP调节子宫内膜再生的机制仍不清楚。在此，我们研究了PRP对子宫内膜再生的治疗作用及可能机制。通过假手术、机械损伤子宫内膜并在有或无PRP的情况下处理10天建立IUA动物模型。模型组子宫切片显示退行性改变，子宫内膜腔狭窄，柱状上皮萎缩，子宫内膜腺体数量减少，子宫内膜厚度降低，胶原沉积增加。PRP可改善上述破坏。转录组测序分析显示，视黄醇代谢途径和细胞外基质（ECM）受体相互作用途径在差异表达基因（DEGs）中上调并富集。黑素转铁蛋白（MELTF）是PRP诱导的子宫内膜再生中关键的上调基因，在体内和体外均得到验证。PRP处理的 Ishikawa 细胞中，铁死亡、自噬和焦亡下调。总之，PRP通过上调视黄醇代谢和与MELTF相关的ECM受体相互作用途径促进子宫内膜再生。同时，PRP还可通过调节铁死亡、自噬和焦亡来抑制子宫内膜上皮细胞死亡。
