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端粒维持如何影响子宫内膜异位症的发展:一项初步研究。

How telomere maintenance affects endometriosis development: a preliminary study.

作者信息

Zhao Xiaoling, Kong Weimin, Luo Dan, Xie Yunkai, Zhang He

机构信息

Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China.

Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

出版信息

Int J Med Sci. 2025 Mar 24;22(8):1944-1957. doi: 10.7150/ijms.102646. eCollection 2025.

Abstract

Endometriosis results in dysmenorrhea, dyspareunia, chronic pelvic pain and infertility in reproductive-age women. However, no effective treatment methods have been applied to the disease, and the pathogenesis of endometriosis is unclear. This study was performed to investigate the association between telomere maintenance and endometriosis development. The telomere length of the postmenopausal endometria, eutopic endometria and their matched ectopic lesions in the proliferative and secretory phases was detected using fluorescence in situ hybridization (FISH) methods, and the effect of telomere length maintenance on the proliferation of endometrial cells derived from endometriotic patients was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BIBR1532 treatment. Then all of the telomere maintenance genes were extracted from the Telnet database, and bioinformatics analysis was performed to uncover the role of telomere maintenance genes in endometriosis development. Telomere length was longer in endometriotic patients' eutopic endometria during the proliferative and secretory phases, and treatment with a telomerase inhibitor inhibited the proliferation of epithelial cells and stromal cells. Furthermore, the telomere maintenance genes were enriched in several hormone-related pathways, with several genes differentially expressed between normal endometria and endometria derived from endometriotic patients. The nomogram constructed based on telomere maintenance genes also displayed good predictive value. Telomere maintenance may contribute to the development of endometriosis, with several related genes involved.

摘要

子宫内膜异位症会导致育龄期女性出现痛经、性交困难、慢性盆腔疼痛和不孕。然而,目前尚无有效的治疗方法应用于该疾病,且子宫内膜异位症的发病机制尚不清楚。本研究旨在探讨端粒维持与子宫内膜异位症发生发展之间的关联。采用荧光原位杂交(FISH)方法检测绝经后子宫内膜、在位内膜及其在增殖期和分泌期的配对异位病灶的端粒长度,并通过用BIBR1532处理的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定端粒长度维持对子宫内膜异位症患者来源的子宫内膜细胞增殖的影响。然后从Telnet数据库中提取所有端粒维持基因,并进行生物信息学分析以揭示端粒维持基因在子宫内膜异位症发生发展中的作用。在增殖期和分泌期,子宫内膜异位症患者的在位内膜端粒长度较长,端粒酶抑制剂处理可抑制上皮细胞和基质细胞的增殖。此外,端粒维持基因在几个与激素相关的途径中富集,正常子宫内膜与子宫内膜异位症患者来源的子宫内膜之间有几个基因差异表达。基于端粒维持基因构建的列线图也显示出良好的预测价值。端粒维持可能有助于子宫内膜异位症的发生发展,涉及多个相关基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b9/11983314/7e297b31daeb/ijmsv22p1944g001.jpg

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