Nasiri Nahid, Babaei Sara, Moini Ashraf, Eftekhari-Yazdi Poopak
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
J Reprod Infertil. 2021 Oct-Dec;22(4):227-240. doi: 10.18502/jri.v22i4.7648.
Inflammation and its master regulator, Nuclear Factor-kB (NF-kB), have been implicated in the development of endometriosis. Inhibition of NF-kB pathway using small molecules ameliorated disease progression and reduced the lesion size; nevertheless, the underlying mechanism is not fully understood. Therefore, this study, is an attempt to assess whether inhibiting NF-kB signaling by aloe-emodin (AE) or aspirin (Asp), as anti-inflammatory compounds, can suppresses the invasive activity of human endometrial stromal cells at stage IV endometriosis.
The eutopic and healthy endometrial biopsies from a total of 8 infertile women with confirmed endometriosis and 8 women without endometriosis were digested and the single cells were cultured. Gene and protein markers of proliferation, migration, adhesion, and invasion of eutopic endometrial stromal cells (EuESCs) with and without treatment with AE or Asp, as well as control endometrial stromal cells (CESCs) was analyzed using q-PCR and immunofluorescence staining, respectively. Comparison between groups was performed using one-way ANOVA and the Bonferroni post hoc and p≤0.5 was considered statistically significant.
There was an association between NF-kB overexpression and higher proliferation/adhesion capacity in EuESCs. EuESCs (at stage IV endometriosis) displayed no invasive and migratory behaviors. Pre-treatment of EuESCs with AE or Asp significantly attenuated NF-kB expression and reduced proliferative, adhesive, invasive, and migratory activity of endometrial cells (p≤0.5).
Eutopic endometrial stromal cells seem to have a semi-invasive activity which is largely suppressed by AE or Asp. It can be suggested that both Asp and AE (as potent NF-kB inhibitors) can be used as a supplement in conventional endometriosis treatments.
炎症及其主要调节因子核因子-κB(NF-κB)与子宫内膜异位症的发生发展有关。使用小分子抑制NF-κB信号通路可改善疾病进展并减小病变大小;然而,其潜在机制尚未完全明确。因此,本研究旨在评估作为抗炎化合物的芦荟大黄素(AE)或阿司匹林(Asp)抑制NF-κB信号传导是否能抑制IV期子宫内膜异位症患者子宫内膜基质细胞的侵袭活性。
收集8例确诊为子宫内膜异位症的不孕女性和8例无子宫内膜异位症女性的在位及健康子宫内膜活检组织,进行消化并培养单细胞。分别采用q-PCR和免疫荧光染色分析在位子宫内膜基质细胞(EuESCs)在接受AE或Asp处理以及未处理情况下,以及对照子宫内膜基质细胞(CESCs)的增殖、迁移、黏附和侵袭的基因及蛋白标志物。组间比较采用单因素方差分析和Bonferroni事后检验,p≤0.5被认为具有统计学意义。
EuESCs中NF-κB过表达与较高的增殖/黏附能力相关。EuESCs(IV期子宫内膜异位症)未表现出侵袭和迁移行为。用AE或Asp预处理EuESCs可显著减弱NF-κB表达,并降低子宫内膜细胞的增殖、黏附、侵袭和迁移活性(p≤0.5)。
在位子宫内膜基质细胞似乎具有半侵袭活性,而AE或Asp可在很大程度上抑制这种活性。可以认为,Asp和AE(作为有效的NF-κB抑制剂)均可作为传统子宫内膜异位症治疗的补充药物。