Rivera-Arce Luis A, Cruz Myrella L, Rodriguez-Cintron Ulises, Torres-Pirela James P, Appleyard Caroline B
Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico.
BMC Womens Health. 2024 Dec 21;24(1):647. doi: 10.1186/s12905-024-03480-7.
Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, and among these are found dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. GI issues such as painful bowel movements, bloating and constipation or diarrhea, are one of the common reasons for misdiagnosis with irritable bowel syndrome (IBS). Enteric glial cells (EGC) are known to play a role in pain associated with IBS, and reactive gliosis has been reported in patients with IBS, but the role of EGC in endometriosis has yet to be elucidated. We hypothesized that endometriosis will induce reactive gliosis, with increased expression of the glial fibrillary acidic protein (GFAP) and S100B, in the myenteric plexus of colonic sections in an animal model of endometriosis.
In the present study animal experiments were employed to explore the impact of endometriosis on the gastrointestinal tract. Using a surgically induced endometriosis rat model, we collected ileal and colonic segments for analysis. We used H&E to assess microscopic damage in colon and ileum, immunofluorescence to measure GFAP and S100B expression in the colon, and toluidine blue staining to measure mast cell infiltration in colon and ileum. Immunofluorescence images were captured using confocal microscope and analyzed using ImageJ software.
All endometriosis animals developed vesicles. These animals had a significant increase in the colonic macroscopic damage compared to Sham and Naïve controls. Colonic and ileal sections didn't show statistical differences in microscopic damage between groups, yet endometriosis ileum had significantly increased mast cell infiltration compared to Naïve. GFAP immunostaining showed significantly increased integrated density in endometriosis when compared to Sham or Naïve, while no statistical difference was found in S100B integrated density between groups.
We conclude that endometriosis can alter GI homeostasis by inducing colon inflammation, reactive gliosis, and ileal mast cell infiltration. Taken together this suggests endometriosis can mimic IBS histopathology beyond the symptomatology, reinforcing this disease's complexity and the need to treat it beyond the gynecological setting.
子宫内膜异位症是一种复杂的妇科疾病,其特征是子宫内膜组织的异位生长。已知子宫内膜异位症的症状会损害患者的生活质量,其中包括痛经、慢性盆腔疼痛和胃肠道(GI)问题。诸如排便疼痛、腹胀以及便秘或腹泻等胃肠道问题,是误诊为肠易激综合征(IBS)的常见原因之一。已知肠胶质细胞(EGC)在与IBS相关的疼痛中起作用,并且在IBS患者中已报道有反应性胶质增生,但EGC在子宫内膜异位症中的作用尚未阐明。我们假设在子宫内膜异位症动物模型中,子宫内膜异位症会在结肠切片的肌间神经丛中诱导反应性胶质增生,同时胶质纤维酸性蛋白(GFAP)和S100B的表达增加。
在本研究中,采用动物实验来探究子宫内膜异位症对胃肠道的影响。使用手术诱导的子宫内膜异位症大鼠模型,我们收集回肠和结肠段进行分析。我们使用苏木精和伊红(H&E)来评估结肠和回肠的微观损伤,免疫荧光法来测量结肠中GFAP和S100B的表达,以及甲苯胺蓝染色来测量结肠和回肠中的肥大细胞浸润。使用共聚焦显微镜拍摄免疫荧光图像,并使用ImageJ软件进行分析。
所有子宫内膜异位症动物均出现水疱。与假手术组和未处理对照组相比,这些动物的结肠宏观损伤显著增加。结肠和回肠切片在各组之间的微观损伤上未显示出统计学差异,但与未处理组相比,子宫内膜异位症回肠中的肥大细胞浸润显著增加。与假手术组或未处理组相比,GFAP免疫染色显示子宫内膜异位症组的积分光密度显著增加,而各组之间S100B积分光密度未发现统计学差异。
我们得出结论,子宫内膜异位症可通过诱导结肠炎症、反应性胶质增生和回肠肥大细胞浸润来改变胃肠道稳态。综上所述,这表明子宫内膜异位症在症状学之外还可模拟IBS的组织病理学,凸显了该疾病的复杂性以及在妇科环境之外进行治疗的必要性。