Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11646. Epub 2020 Nov 12.
Estrogen is a commonly used hormone in the adjuvant treatment of intrauterine adhesion (IUA), which can promote endometrial growth. Stem cell transplantation has also been reported to promote endometrial regeneration in IUA due to its potential differentiative capacity. Human Wharton's jelly mesenchymal stem cells (WJ‑MSCs) are isolated from the umbilical cord, possess strong self‑renewal and proliferative abilities, and are hypo‑immunogenic and non‑tumorigenic. Therefore, the present study aimed to investigate the therapeutic effects and underlying mechanism of WJ‑MSCs transplantation with estrogen treatment, separately or as a combined therapy, on IUA. The IUA model was established using the ethanol damage method. A total of 50 Sprague‑Dawley female rats were randomly divided into the control, IUA model, WJ‑MSCs treatment, estrogen treatment and WJ‑MSCs+ estrogen treatment groups (n=10/group). WJ‑MSCs were injected three times at 5‑day intervals. IUA rats in the estrogen group received 0.2 mg/kg estrogen through intragastric administration, once every 2 days for 8 weeks. Morphological changes were evaluated by hematoxylin‑eosin staining. Immunohistochemical evaluations of pan‑keratin, vimentin, transforming growth factor (TGF)‑β1, RhoA, RhoB, RhoC, Rho‑associated coiled‑coil‑containing protein kinase (ROCK)I, and ROCKII expression were performed in uterine tissue. After treatment, the uterine specimens were observed to have increased uterine thickness and gland numbers in all treatment groups compared with the IUA group; however, the degree of restoration in the independent WJ‑MSCs and estrogen treatment groups was better than in the combined treatment group. Immunohistochemical analysis demonstrated that pan‑keratin expression was increased, and RhoA, ROCKI and TGF‑β1 expression was significantly inhibited in the WJ‑MSCs and WJ‑MSCs + estrogen treatment groups compared with the IUA group; however, the expression levels of these proteins were similar among all treatment groups. No change in vimentin expression was detected in any treatment group. The expression levels of RhoB, RhoC and ROCKII were clearly not affected by WJ‑MSCs intervention alone. In conclusion, transplantation of WJ‑MSCs may repair endometrial damage in IUA rats via TGF‑β1‑mediated inhibition of RhoA/ROCKI signaling.
雌激素是宫腔粘连（IUA）辅助治疗中常用的激素，可促进子宫内膜生长。有报道称，干细胞移植也能促进 IUA 中的子宫内膜再生，这与其潜在的分化能力有关。人脐带来源的间充质干细胞（WJ-MSCs）分离自脐带，具有较强的自我更新和增殖能力，免疫原性低，无致瘤性。因此，本研究旨在探讨 WJ-MSCs 联合雌激素治疗与单独雌激素治疗或 WJ-MSCs 治疗对 IUA 的治疗效果及作用机制。采用乙醇损伤法建立 IUA 模型。将 50 只雌性 Sprague-Dawley 大鼠随机分为对照组、IUA 模型组、WJ-MSCs 治疗组、雌激素治疗组和 WJ-MSCs+雌激素治疗组（每组 10 只）。WJ-MSCs 于 5 天间隔内分 3 次注射。雌激素组大鼠通过灌胃给予 0.2mg/kg 雌激素，每 2 天 1 次，共 8 周。苏木精-伊红染色评估形态学变化。对子宫组织中 pan-角蛋白、波形蛋白、转化生长因子（TGF）-β1、RhoA、RhoB、RhoC、Rho 相关卷曲螺旋含蛋白激酶（ROCK）I 和 ROCKII 的表达进行免疫组化评价。治疗后，与 IUA 组相比，所有治疗组的子宫标本均显示子宫厚度和腺体数量增加，但独立的 WJ-MSCs 和雌激素治疗组的恢复程度优于联合治疗组。免疫组化分析表明，与 IUA 组相比，WJ-MSCs 和 WJ-MSCs+雌激素治疗组 pan-角蛋白表达增加，RhoA、ROCKI 和 TGF-β1 表达明显受到抑制，但所有治疗组的这些蛋白表达水平相似。任何治疗组的波形蛋白表达均无变化。WJ-MSCs 干预单独对 RhoB、RhoC 和 ROCKII 的表达水平没有明显影响。综上所述，WJ-MSCs 移植可能通过 TGF-β1 介导的抑制 RhoA/ROCKI 信号通路修复 IUA 大鼠的子宫内膜损伤。
