Transcriptomic changes in eutopic endometrium and ectopic lesions during endometriosis progression in a mouse model

Rong Li Ph.D. , Dinh Nam Tran Ph.D. , Bruce A. Lessey M.D., Ph.D. , Steven L. Young M.D., Ph.D. , Tae Hoon Kim Ph.D. , Jae-Wook Jeong Ph.D.
{"title":"Transcriptomic changes in eutopic endometrium and ectopic lesions during endometriosis progression in a mouse model","authors":"Rong Li Ph.D. ,&nbsp;Dinh Nam Tran Ph.D. ,&nbsp;Bruce A. Lessey M.D., Ph.D. ,&nbsp;Steven L. Young M.D., Ph.D. ,&nbsp;Tae Hoon Kim Ph.D. ,&nbsp;Jae-Wook Jeong Ph.D.","doi":"10.1016/j.xfss.2024.02.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To identify the transcriptomic changes of ectopic lesions and eutopic endometrial tissues during the progression of endometriosis, we performed transcriptomic analysis in the eutopic endometrium and ectopic lesions.</p></div><div><h3>Design</h3><p>Laboratory study.</p></div><div><h3>Setting</h3><p>Academic medical center.</p></div><div><h3>Animals</h3><p>Four fertile and 4 subfertile <em>Pgr</em><sup>cre/+</sup><em>Rosa26</em><sup>mTmG/+</sup> mice with endometriosis, and 4 sham mice for each group of endometriosis mice as control. These mice underwent either surgery to induce endometriosis or sham surgery. Fertile sham and mice with endometriosis were used 1 month after surgery, whereas subfertile ones were used 3 months after surgery.</p></div><div><h3>Interventions</h3><p>Early and chronic effects of endometriosis on transcriptomics of ectopic lesions and eutopic endometrium.</p></div><div><h3>Main Outcome Measures</h3><p>RNA-sequencing analysis and identification of differentially expressed genes and pathways in the ectopic lesions and eutopic uteri from mice with endometriosis and sham mice at day 3.5 of pregnancy.</p></div><div><h3>Results</h3><p>Our mouse model recapitulates the transcriptomic changes of ectopic lesions in humans. RNA-sequencing analysis was performed in ectopic lesions and eutopic uteri from mice with or without endometriosis during the progression of the disease. Estrogen activity, inflammation, angiogenesis, and fibrosis pathways were consistently elevated in all the ectopic lesions compared with eutopic endometrium. Cholesterol/glucose synthesis and stem cell pluripotency pathways were more enhanced in ectopic lesions from subfertile mice compared with their eutopic endometrium. Dysregulation of infiltration of macrophage, dendritic, T and B cells was validated with the use of immunohistochemistry in ectopic lesions. Multiple ligand–receptor pairs between the ectopic and eutopic endometrium were altered compared with the sham endometrium. Suppressed WNT and EGF pathways were only found in the eutopic endometrium from subfertile not fertile mice compared with sham.</p></div><div><h3>Conclusions</h3><p>Our mouse endometriosis model recapitulates the transcriptomics of ectopic lesions in humans. Our transcriptomic analysis during endometriosis progression in our mouse model will help us understand the pathophysiology of endometriosis.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 2","pages":"Pages 182-194"},"PeriodicalIF":0.0000,"publicationDate":"2024-05-01","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/S2666335X24000144","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

To identify the transcriptomic changes of ectopic lesions and eutopic endometrial tissues during the progression of endometriosis, we performed transcriptomic analysis in the eutopic endometrium and ectopic lesions.

Design

Laboratory study.

Setting

Academic medical center.

Animals

Four fertile and 4 subfertile Pgrcre/+Rosa26mTmG/+ mice with endometriosis, and 4 sham mice for each group of endometriosis mice as control. These mice underwent either surgery to induce endometriosis or sham surgery. Fertile sham and mice with endometriosis were used 1 month after surgery, whereas subfertile ones were used 3 months after surgery.

Interventions

Early and chronic effects of endometriosis on transcriptomics of ectopic lesions and eutopic endometrium.

Main Outcome Measures

RNA-sequencing analysis and identification of differentially expressed genes and pathways in the ectopic lesions and eutopic uteri from mice with endometriosis and sham mice at day 3.5 of pregnancy.

Results

Our mouse model recapitulates the transcriptomic changes of ectopic lesions in humans. RNA-sequencing analysis was performed in ectopic lesions and eutopic uteri from mice with or without endometriosis during the progression of the disease. Estrogen activity, inflammation, angiogenesis, and fibrosis pathways were consistently elevated in all the ectopic lesions compared with eutopic endometrium. Cholesterol/glucose synthesis and stem cell pluripotency pathways were more enhanced in ectopic lesions from subfertile mice compared with their eutopic endometrium. Dysregulation of infiltration of macrophage, dendritic, T and B cells was validated with the use of immunohistochemistry in ectopic lesions. Multiple ligand–receptor pairs between the ectopic and eutopic endometrium were altered compared with the sham endometrium. Suppressed WNT and EGF pathways were only found in the eutopic endometrium from subfertile not fertile mice compared with sham.

Conclusions

Our mouse endometriosis model recapitulates the transcriptomics of ectopic lesions in humans. Our transcriptomic analysis during endometriosis progression in our mouse model will help us understand the pathophysiology of endometriosis.

小鼠模型中异位子宫内膜和异位病灶在子宫内膜异位症发展过程中的转录组变化。
目的确定异位病灶和异位子宫内膜组织在子宫内膜异位症进展过程中的转录组变化:我们的假设是,子宫内膜异位症的发展和进展会改变异位内膜和异位病灶的转录组:学术医学中心四只可育和四只亚可育的 Pgrcre/+Rosa26mTmG/+ 子宫内膜异位症小鼠,每组子宫内膜异位症小鼠有四只假小鼠作为对照。这些小鼠要么接受了诱发子宫内膜异位症的手术,要么接受了假手术。肥育假小鼠和子宫内膜异位症小鼠在手术后一个月使用,亚肥育小鼠在手术后三个月使用:干预措施:子宫内膜异位症对异位病灶和异位内膜转录组学的早期和慢性影响:结果:我们的小鼠模型再现了子宫内膜异位症对异位病灶和异位子宫内膜转录组学的早期和慢性影响:我们的小鼠模型再现了人类异位病变的转录组变化。我们对患有或未患有子宫内膜异位症的小鼠异位病灶和异位子宫在疾病进展过程中的转录组变化进行了RNA-seq分析。与异位子宫内膜相比,所有异位病灶中的雌二醇、炎症、血管生成和纤维化通路都持续升高。与异位子宫内膜相比,亚肥育小鼠异位病灶中的胆固醇/葡萄糖合成和干细胞多能性途径更强。异位病灶中巨噬细胞、树突状细胞、T 细胞和 B 细胞的浸润失调通过免疫组化得到了验证。与假性子宫内膜相比,异位和异位子宫内膜的多种配体-受体对发生了改变。与假性内膜相比,仅在亚肥育而非肥育小鼠的异位内膜中发现了受抑制的 WNT 和 EGF 通路:我们的小鼠子宫内膜异位症模型再现了人类异位病变的转录组学。结论:我们的小鼠子宫内膜异位症模型再现了人类异位病变的转录组学,我们在小鼠模型中进行的子宫内膜异位症进展过程中的转录组学分析将有助于了解子宫内膜异位症的病理生理学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
F&S science
F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology
CiteScore
2.00
自引率
0.00%
发文量
0
审稿时长
51 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信