Hapangama D K, Turner M A, Drury J A, Quenby S, Saretzki G, Martin-Ruiz C, Von Zglinicki T
School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK.
Hum Reprod. 2008 Jul;23(7):1511-9. doi: 10.1093/humrep/den172. Epub 2008 May 2.
In order to test our hypothesis that endometriosis is associated with abnormal expression of telomerase and telomere lengthening in endometrium, we assessed endometrial expression of the human telomerase enzyme and telomere length (TL).
This prospective pilot study, included 29 women with symptomatic, surgically diagnosed endometriosis (Group 1) and 27 healthy, fertile, symptom-free women without endometriosis (Group 2, confirmed by laparoscopy). Seventeen women in Group 1 and 15 women in Group 2 had endometrial biopsies taken on Day 21 +/- 2 of the cycle. A further 12 women in each group were biopsied on Day 26 +/- 2. Telomerase and estrogen receptor beta (ERbeta) expression was evaluated by immunohistochemistry. Mean TL was determined by quantitative PCR.
The endometria of fertile healthy women showed either weak or no telomerase immunoreactivity throughout the luteal phase. Immunostaining for telomerase was significantly increased during the implantation window and the premenstrual endometria of women with endometriosis (P < 0.0001). This was associated with a loss of stromal and vascular ERbeta immunostaining (P < 0.05). The mean TL were significantly longer in endometria of women with endometriosis during the implantation window (P = 0.005), indicating the biological relevance of our novel finding of telomerase in benign endometrium. There was positive correlation of the circulating estradiol with peripheral blood TL in women.
We speculate that aberrant endometrial expression of telomerase mediates alterations in cell fate that enhance proliferation, contributing to the pathogenesis of endometriosis.
为了验证我们的假设,即子宫内膜异位症与子宫内膜中端粒酶异常表达及端粒延长有关,我们评估了人端粒酶和端粒长度(TL)在子宫内膜中的表达。
这项前瞻性初步研究纳入了29例有症状、经手术诊断为子宫内膜异位症的女性(第1组)和27例健康、可育、无症状且无子宫内膜异位症的女性(第2组,经腹腔镜检查确诊)。第1组中的17例女性和第2组中的15例女性在月经周期的第21±2天进行了子宫内膜活检。每组另有12例女性在第26±2天进行活检。通过免疫组织化学评估端粒酶和雌激素受体β(ERβ)的表达。通过定量PCR测定平均TL。
在整个黄体期,可育健康女性的子宫内膜显示端粒酶免疫反应性较弱或无反应性。在植入窗期和子宫内膜异位症女性的经前子宫内膜中,端粒酶免疫染色显著增加(P<0.0001)。这与基质和血管ERβ免疫染色的丧失有关(P<0.05)。在植入窗期,子宫内膜异位症女性的子宫内膜平均TL显著更长(P=0.005),表明我们在良性子宫内膜中发现端粒酶这一新颖发现具有生物学相关性。女性循环雌二醇与外周血TL呈正相关。
我们推测,端粒酶在子宫内膜中的异常表达介导了细胞命运的改变,增强了增殖,从而导致子宫内膜异位症的发病机制。