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

Rong Li, Dinh Nam Tran, Bruce A Lessey, Steven L Young, Tae Hoon Kim, Jae‐Wook Jeong, Jae-Wook Jeong
F&S science · 2024 · vol. 5(2) , pp. 182–194 · doi:10.1016/j.xfss.2024.02.001 · PMID:38342342 · PMC11116064 · W4391685971
article OA: gold CC0 ⤵ 3 in-corpus citations
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Transcriptomic analysis of a mouse endometriosis model revealed elevated estrogen activity, inflammation, angiogenesis, and fibrosis in ectopic lesions, with enhanced cholesterol/glucose synthesis and stem cell pluripotency in subfertile mice.

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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.

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Condition tags

endometriosis

MeSH descriptors

Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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Cited by (3)

SciLite annotations

organisms 30
yim 93624 mus sp. mus sp. mus sp. mus sp. humans transgenic mice transgenic mice multicellular animals mus sp. mus sp. transgenic mice human mus sp. transgenic mice rodents primates papio papio sensu groves rhesus monkeys humans human primates transgenic mice mus sp. rodents noordeloos 2009062 onychomys naine d'afrique de l'ouest rabbits horseradish
chemicals 13
formaldehyde cholesterol glucose estradiol estrogen progesterone steroid estradiol haematoxylin cholesterol glucose lipoprotein prostaglandin

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