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

Abstract

ObjectiveTo identify the transcriptomic changes of ectopic lesions and eutopic endometrial tissues during the progression of endometriosis. HypothesisOur hypothesis is that development and progression of endometriosis change transcriptome in the eutopic endometrium and ectopic lesions DesignLaboratory study. SettingAcademic Medical Center AnimalsFour fertile and four subfertile Pgrcre/+Rosa26mTmG/+ mice with endometriosis, and four 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 one month after surgery, while subfertile ones were used three months after surgery. InterventionsEarly and chronic effect of endometriosis on transcriptomics of ectopic lesions and eutopic endometrium Main Outcome MeasuresRNA-Sequencing analysis (RNA-Seq) and identification of differential expressed genes and pathways in the ectopic lesions and eutopic uteri from mice with endometriosis and sham mice at day of pregnancy 3.5. ResultsOur mouse model recapitulates the transcriptomic changes of ectopic lesions in human. RNA-seq was performed in ectopic lesions and eutopic uteri from mice with or without endometriosis during progression of disease. Estradiol, inflammation, angiogenesis, and fibrosis pathways were consistently elevated in all the ectopic lesions compared to eutopic endometrium. Cholesterol/glucose synthesis and stem cell pluripotency pathways were more enhanced in ectopic lesions from subfertile mice compared to their eutopic endometrium. Dysregulation of infiltration of macrophage, dendritic, T and B cells were validated by using immunohistochemistry in ectopic lesions. multiple ligand-receptor pairs between the ectopic and eutopic endometrium were altered compared to the sham endometrium. Suppressed WNT and EGF pathways were only found in the eutopic endometrium from subfertile not fertile mice compared to sham. ConclusionsOur mouse endometriosis model recapitulates the transcriptomics of ectopic lesions in humans. Our transcriptomic analysis during endometriosis progression in our mouse model will help understand the pathophysiology of endometriosis.