{"title":"Role of tenascin C in lesion formation in early peritoneal endometriosis","authors":"Maako Moriyama M.D. , Kazuomi Nakamura Ph.D. , Hiroki Nagata M.D. , Ikumi Wada M.D. , Kei Nagira M.D., Ph.D. , Yukihiro Azuma M.D., Ph.D. , Eri Sato M.D., Ph.D. , Tasuku Harada M.D., Ph.D. , Fuminori Taniguchi M.D., Ph.D.","doi":"10.1016/j.xfss.2023.12.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p><span>To identify cytokines or extracellular matrix<span> components that contribute to adhesion to, and invasion of, the peritoneum, proximal to lesions in the early phase of </span></span>endometriosis.</p></div><div><h3>Design</h3><p>Laboratory-based study.</p></div><div><h3>Setting</h3><p>University Hospital and Laboratory of Animal Science.</p></div><div><h3>Patients and Animals</h3><p><span>Five women with ovarian endometrioma, 138 wild-type (WT) C57BL/6N mice, and 48 </span><span><em>Tenascin</em><em> C</em></span> (<em>Tnc</em>) knockout (TncKO) mice.</p></div><div><h3>Interventions</h3><p><span><span>To establish a murine endometriosis model, 20 pieces of minced uterine tissue fragments from each horn were administered intraperitoneally to syngeneic mice. Three days later, endometriotic lesions and peritoneal tissues were collected. Separately, we transfected human peritoneal </span>mesothelial cells<span> (HMrSV5) or human endometrial stromal cells (hESCs) with </span></span><em>Tnc</em><span> small interfering ribonucleic acid.</span></p></div><div><h3>Main Outcome Measures</h3><p><span>We employed a polymerase chain reaction<span> array to profile gene expression in the murine peritoneum, in both peritoneum distal to lesions and peritoneum surrounding lesions (PSL). The expression of upregulated genes in the PSL was verified in the peritoneal samples by real-time reverse transcription-polymerase chain reaction. TncKO mice were used to investigate the role of Tnc in the development of endometriosis. We evaluated the proliferative activity or inflammatory state of lesions by Ki67 or CD3 immunostaining. Intraperitoneal distribution of macrophages was assessed by fluorescence-activated cell sorting. Using </span></span><em>Tnc</em> small interfering ribonucleic acid, we examined the invasive capacity of hESCs in a coculture system with HMrSV5.</p></div><div><h3>Results</h3><p><em>Tnc</em> gene expression was significantly higher in PSL than in peritoneum distal to lesions. The weight and number of TncKO lesions in TncKO hosts were lower than those of WT lesions in WT hosts. In contrast, the weight and number of nonattached TncKO lesions in TncKO hosts were higher than those of nonattached WT lesions in WT hosts. We observed decreased Ki67-positive cells or H-scores for CD3, a lower proportion of M1 macrophages, and a higher proportion of M2 macrophages in TncKO lesions in TncKO recipients. Silencing of <em>Tnc</em> expression in hESCs and HMrSV5 diminished the invasivity of hESCs.</p></div><div><h3>Conclusion</h3><p><em>Tnc</em> may be a crucial factor in the development of early peritoneal endometriosis.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 1","pages":"Pages 69-79"},"PeriodicalIF":0.0000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666335X23000757","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Objective
To identify cytokines or extracellular matrix components that contribute to adhesion to, and invasion of, the peritoneum, proximal to lesions in the early phase of endometriosis.
Design
Laboratory-based study.
Setting
University Hospital and Laboratory of Animal Science.
Patients and Animals
Five women with ovarian endometrioma, 138 wild-type (WT) C57BL/6N mice, and 48 Tenascin C (Tnc) knockout (TncKO) mice.
Interventions
To establish a murine endometriosis model, 20 pieces of minced uterine tissue fragments from each horn were administered intraperitoneally to syngeneic mice. Three days later, endometriotic lesions and peritoneal tissues were collected. Separately, we transfected human peritoneal mesothelial cells (HMrSV5) or human endometrial stromal cells (hESCs) with Tnc small interfering ribonucleic acid.
Main Outcome Measures
We employed a polymerase chain reaction array to profile gene expression in the murine peritoneum, in both peritoneum distal to lesions and peritoneum surrounding lesions (PSL). The expression of upregulated genes in the PSL was verified in the peritoneal samples by real-time reverse transcription-polymerase chain reaction. TncKO mice were used to investigate the role of Tnc in the development of endometriosis. We evaluated the proliferative activity or inflammatory state of lesions by Ki67 or CD3 immunostaining. Intraperitoneal distribution of macrophages was assessed by fluorescence-activated cell sorting. Using Tnc small interfering ribonucleic acid, we examined the invasive capacity of hESCs in a coculture system with HMrSV5.
Results
Tnc gene expression was significantly higher in PSL than in peritoneum distal to lesions. The weight and number of TncKO lesions in TncKO hosts were lower than those of WT lesions in WT hosts. In contrast, the weight and number of nonattached TncKO lesions in TncKO hosts were higher than those of nonattached WT lesions in WT hosts. We observed decreased Ki67-positive cells or H-scores for CD3, a lower proportion of M1 macrophages, and a higher proportion of M2 macrophages in TncKO lesions in TncKO recipients. Silencing of Tnc expression in hESCs and HMrSV5 diminished the invasivity of hESCs.
Conclusion
Tnc may be a crucial factor in the development of early peritoneal endometriosis.