Department of Obstetrics and Gynecology, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye
Department of General Surgery, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye
Balkan Med J. 2024 Oct 31;41(6):484-490. doi: 10.4274/balkanmedj.galenos.2024.2024-6-95. Epub 2024 Sep 18.
Endometriosis (EM) is an inflammatory condition in which the endometrium is observed to develop outside the uterine cavity. Endometrium has conventionally been recognized as a rich source of endometrial mesenchymal stem cells (E-MSCs). The influence of dienogest, a medication frequently prescribed for EM, on E-MSCs has not been extensively investigated.
To explore effects of dienogest on the E-MSCs derived from healthy (E-MSCs-control) and diseased (E-MSCs-endometriosis) endometrial tissue samples in vitro.
In vitro study.
We collected samples from healthy and diseased endometrial tissues. E-MSCs were derived from both healthy and EM tissues. The effect of dienogest (VISANNE) on E-MSCs was assessed by examining cell proliferation, telomerase activity, cell migration, and estrogen secretion levels after the isolation and characterization of E-MSCs.
We discovered that cellular proliferation rate was higher in the E-MSCs derived from EM tissues compared to those derived from healthy tissue. The proliferation rate and telomerase activity were both suppressed by dienogest treatment, particularly in E-MSCs-endometriosis. The drug treatment also resulted in a decrease in the migration capacity of E-MSCs-endometriosis, from 60.4% to 59.2%. The expression of CXCL12, Ki67, and beta-catenin was analyzed in both E-MSCs-endometriosis and E-MSCs-control. The CXCL12 and Ki67 expressions were quite elevated in the E-MSCs-endometriosis without drug treatment compared to the E-MSCs-control. Following the treatment, these levels declined drastically to the levels close to E-MSCs-control. Similarly, this decrease in gene expression was accompanied by a decrease in estrogen secretion into the medium.
This research demonstrates that dienogest exerts a substantial impact on both stromal and stem cells, as it effectively controls the disease by reversing EM markers, despite the absence of progesterone receptors on endometrial stem cells.
子宫内膜异位症（EM）是一种炎症性疾病，子宫内膜被观察到在子宫腔外发育。子宫内膜通常被认为是子宫内膜间充质干细胞（E-MSCs）的丰富来源。地诺孕素对 E-MSCs 的影响尚未得到广泛研究，地诺孕素是一种常用于治疗 EM 的药物。
探讨地诺孕素对体外来源于健康（E-MSCs-对照）和疾病（E-MSCs-子宫内膜异位症）子宫内膜组织样本的 E-MSCs 的影响。
体外研究。
我们从健康和疾病的子宫内膜组织中采集样本。从健康和 EM 组织中分离出 E-MSCs。通过检查 E-MSCs 分离和鉴定后细胞增殖、端粒酶活性、细胞迁移和雌激素分泌水平，评估地诺孕素（维斯安）对 E-MSCs 的影响。
我们发现，来源于 EM 组织的 E-MSCs 的细胞增殖率高于来源于健康组织的 E-MSCs。地诺孕素处理抑制了细胞增殖率和端粒酶活性，尤其是在 E-MSCs-子宫内膜异位症中。药物治疗还导致 E-MSCs-子宫内膜异位症的迁移能力下降，从 60.4%降至 59.2%。分析了 E-MSCs-子宫内膜异位症和 E-MSCs-对照中 CXCL12、Ki67 和β-连环蛋白的表达。未经药物治疗的 E-MSCs-子宫内膜异位症中 CXCL12 和 Ki67 的表达明显高于 E-MSCs-对照。治疗后，这些水平急剧下降到接近 E-MSCs-对照的水平。同样，这种基因表达的下降伴随着雌激素分泌到培养基中的减少。
这项研究表明，地诺孕素对基质细胞和干细胞都有很大的影响，因为它通过逆转 EM 标志物有效地控制了疾病，尽管子宫内膜干细胞上缺乏孕激素受体。
