Intrauterine adhesions (IUAs) are characterized by the injury of endometrium due to curettage and/or endometritis. The loss of functional endometrium in uterine cavity usually results in hypomenorrhea, amenorrhea, infertility, and/or recurrent pregnancy loss. Recently, stem cell transplantation has been applied to promote the endometrial regeneration. Human amnion epithelial cells (hAECs) have been shown to have stem cell characteristics. In this study, we found that PKH26-labeled hAECs were mainly distributed in the basal layer of endometrium after transplantation, and hAEC transplantation, including uterine injection and tail vein injection, could increase pregnancy rate and the number of embryos in rat model of IUAs. Moreover, hAEC transplantation was demonstrated to increase the endometrial thickness, promote the proliferation of glands and blood vessels, and decrease fibrotic areas in the endometrium. The immunohistochemical and quantitative polymerase chain reaction analysis showed the upregulated expression of growth factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) after hAEC transplantation; and the downregulated expression of collagen type I alpha 1 (COL1A1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-β (TGF-β), all of which are associated with the extracellular matrix (ECM) deposition after hAEC transplantation. The mRNA sequencing indicated that platelet-derived growth factor-C (PDGF-C), thrombospondin-1 (THBS1), connective tissue growth factor (CTGF), Wnt5a, and Snai2 were significantly modulated in treatment groups. These results indicate that hAEC transplantation promotes endometrial regeneration and the restoration of fertility in rat model of IUAs.

中文翻译：

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人羊膜上皮细胞移植改善子宫内膜粘连大鼠模型的子宫内膜再生。

宫腔粘连 (IUAs) 的特征是由于刮宫和/或子宫内膜炎引起的子宫内膜损伤。子宫腔内功能性子宫内膜的丧失通常会导致月经过多、闭经、不孕和/或反复流产。最近，干细胞移植已被应用于促进子宫内膜再生。人类羊膜上皮细胞 (hAEC) 已被证明具有干细胞特征。本研究发现PKH26标记的hAECs主要分布于移植后子宫内膜基底层，hAEC移植包括子宫注射和尾静脉注射，可提高IUA大鼠模型的妊娠率和胚胎数量。此外，hAEC 移植被证明可以增加子宫内膜厚度，促进腺体和血管的增殖，减少子宫内膜的纤维化区域。免疫组化和定量聚合酶链反应分析显示，hAEC移植后碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、胰岛素样生长因子-1（IGF-1）等生长因子表达上调；和 I 型 α 1 型胶原蛋白 (COL1A1)、金属蛋白酶-1 组织抑制剂 (TIMP-1) 和转化生长因子-β (TGF-β) 的表达下调，所有这些都与细胞外基质 (ECM) 相关hAEC 移植后的沉积。mRNA 测序表明血小板衍生生长因子-C (PDGF-C)、血小板反应蛋白-1 (THBS1)、结缔组织生长因子 (CTGF)、Wnt5a、和 Snai2 在治疗组中受到显着调节。这些结果表明，hAEC 移植促进了 IUA 大鼠模型的子宫内膜再生和生育能力的恢复。