Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Shuaifuyuan Wangfujing, Dongcheng, PR China.
Exp Biol Med (Maywood). 2012 Nov;237(11):1350-8. doi: 10.1258/ebm.2012.012060.
Endometriosis, with a prevalence rate ranging from 6% to 10%, is the major contributor to pelvic pain and subfertility, and considerably reduces the quality of life in affected women. However, the pathogenesis of this disease remains largely unknown. The present study aimed to uncover the role of hyperperistalsis in the pathogenesis of endometriosis, by exploring the response of human endometrial stromal cells (ESCs) to the cyclic stretch in vitro. ESCs isolated from 18 different endometrium biopsies undergoing hysterectomy for myoma were subjected to uniaxial cyclic stretches with different magnitude and frequency using the Uniaxial Tension System. Expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in stretched and unstretched ESCs were assessed by realtime quantitative polymerase chain reaction and Western blot. Production of prostaglandin E2 (PGE(2)) in the culture medium was measured by enzyme-linked immunosorbent assay. The cyclic stretch mimicking hyperperistalsis in endometriosis (5% elongation at 4 cycles/min) stimulated quick up-regulations of COX-2 and mPGES-1 simultaneously on both transcriptional and translational levels, and delayed PGE(2) overproduction was also noted in ESCs. As the stretch magnitude or frequency increased, so did overexpression of COX-2 and PGE(2) (P < 0.05). By contrast, the cyclic stretch mimicking physiological peristalsis (3% elongation at 2 cycles/min) did not induce significant COX-2, mPGES-1 or PGE(2) production within 12 h. Both COX-2 and mPEGS-1 are PGE(2) synthases, and the aberrant COX-2 and PGE(2) production play important roles in the pathogenesis of endometriosis. Therefore, the present findings revealed that increased stretch stimuli from the hyperperistalsis of endometriosis were capable of causing the aberrant COX-2 and PGE(2) expression in the endometrium by mechanotransduction, in a magnitude and frequency-dependent manner. It implied possible roles of hyperperistalsis in the pathogenesis of endometriosis, particularly in the view of COX-2 and PGE(2).
子宫内膜异位症的患病率为 6%至 10%，是导致盆腔疼痛和不孕的主要原因，并显著降低了受影响女性的生活质量。然而，这种疾病的发病机制在很大程度上仍然未知。本研究旨在通过研究体外人类子宫内膜基质细胞（ESC）对周期性拉伸的反应，揭示蠕动过度在子宫内膜异位症发病机制中的作用。从因子宫肌瘤接受子宫切除术的 18 个不同子宫内膜活检中分离 ESC，使用单轴张力系统对 ESC 进行不同幅度和频率的单轴循环拉伸。通过实时定量聚合酶链反应和 Western blot 评估拉伸和未拉伸 ESC 中环氧化酶-2（COX-2）和微粒体前列腺素 E2 合酶-1（mPGES-1）的表达。通过酶联免疫吸附试验测量培养基中前列腺素 E2（PGE（2））的产生。模拟子宫内膜异位症蠕动过度的循环拉伸（4 个循环/分钟时 5%伸长）同时在转录和翻译水平上快速上调 COX-2 和 mPGES-1，并且还观察到 ESC 中 PGE（2）的延迟过度产生。随着拉伸幅度或频率的增加，COX-2 和 PGE（2）的过表达也增加（P <0.05）。相比之下，模拟生理蠕动的循环拉伸（2 个循环/分钟时 3%伸长）在 12 小时内不会引起 COX-2、mPGES-1 或 PGE（2）的显著产生。COX-2 和 mPEGS-1 都是 PGE（2）合酶，异常的 COX-2 和 PGE（2）产生在子宫内膜异位症的发病机制中起重要作用。因此，本研究结果表明，子宫内膜异位症蠕动过度增加的拉伸刺激能够通过机械转导以幅度和频率依赖的方式引起子宫内膜中异常的 COX-2 和 PGE（2）表达。这暗示了蠕动过度在子宫内膜异位症发病机制中的可能作用，特别是从 COX-2 和 PGE（2）的角度来看。
