The establishment of a mouse model of deep endometriosis

Dingmin Yan, Yan D, Liu X, Xishi Liu, Sun-Wei Guo, Sun‐Wei Guo
Human Reproduction · 2018 · vol. 34(2) , pp. 235–247 · doi:10.1093/humrep/dey361 · PMID:30561644 · W2904382647
Lab / animal OA: bronze CC0 ⤵ 31 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-08 ⓘ

A mouse model of deep endometriosis was established using uterine fragments and neuropeptides, demonstrating macroscopic, microscopic, and molecular characteristics similar to human lesions.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

STUDY QUESTION: Is it possible to establish a mouse model of deep endometriosis (DE)? SUMMARY ANSWER: A mouse DE model that is macroscopically and microscopically similar to nodular lesions in humans can be constructed in as short as 3 weeks by intraperitoneal injection of uterine fragments along with the infusion of substance P (SP) and/or calcitonin gene-related peptide (CGRP). WHAT IS KNOWN ALREADY: Although a baboon DE model was reported 5 years ago, its prohibitive cost and demand for facilities and expertise associated with the use of non-human primates put its use out of reach for most laboratories. STUDY DESIGN, SIZE, DURATION: A total of 48 female Balb/C mice were used for this study. Among them, 16 were randomly selected as donors that contributed uterine fragments, and the remaining 32 were recipient mice. The mice with induced endometriosis were followed up for 3-4 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: One day before the induction of endometriosis by intraperitoneal injection of uterine fragments, osmotic pumps were inserted into equal groups of recipient mice to infuse either sterile saline, SP, CGRP, or both SP and CGRP. The hotplate test was administrated to all mice at the baseline and before and after induction of endometriosis. Four (3 for the SP+CGRP group) weeks after induction, all mice were sacrificed. Their endometriotic lesions were excised, weighed and processed for histopathologic examination, and histochemistry, immunohistochemistry and immunofluorescence analyses of markers of proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), mesothelial-mesenchymal transition (MMT) and endothelial-mesenchymal transition (EndoMT) were done. The extent of lesional fibrosis was evaluated by Masson trichrome staining. To further evaluate surrounding organ/tissue invasion, the peritoneal areas adhesive to the lesions were excised for immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Endometriotic lesions in mice treated with SP and/or CGRP satisfied all requirements for DE, i.e. presence of endometrial epithelial and stromal cells, abundance of fibromuscular content, and encapsulation in surrounding tissues or organs. The lesion weight in the CGRP, SP and SP+CGRP groups was 1.62, 2.14 and 2.18-fold, respectively, heavier than that of control group. Concomitantly, the SP, CGRP and SP+CGRP groups had significantly shorter hotplate latency than that of control group. Lesions in mice treated with SP and/or CGRP, especially with SP+CGRP, exhibited characteristics consistent with EMT, FMT, SMM and extensive fibrosis, along with signs of MMT and EndoMT. Lesional invasion into surrounding tissues/organs was found to be 25.0, 75.0 and 87.5% in mice treated with CGRP, SP and SP+CGRP, but none in control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of histologic and immunohistochemistry analyses only and lacks molecular data. WIDER IMPLICATIONS OF THE FINDINGS: The establishment of a mouse DE model supports the idea that endometriotic lesions are wounds undergoing repeated tissue injury and repair and underscores the importance of microenvironments in shaping the lesions' destiny. In addition, signs consistent with MMT and EndoMT indicate that there may be more culpable factors that still remain unidentified and should be pursued in the future. Moreover, the close correlation between the extent of lesional fibrosis and markers of EMT, MMT, EndoMT, FMT and SMM as shown here should facilitate our understanding of the molecular mechanisms underlying the DE pathophysiology. Since this DE model is based on a biologically plausible and evidence-backed theory, it should shed much needed insight into the molecular mechanisms underlying the pathophysiology of DE. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Grants 81471434 (S.W.G.), 81530040 (S.W.G.), 81771553 (S.W.G.), 81671436 (X.S.L.) and 81871144 (X.S.L.) from the National Natural Science Foundation of China. None of the authors has any conflict of interest to disclose.

My notes (saved in your browser only)

Condition tags

endometriosis

MeSH descriptors

Disease Models, Animal Disease Models, Animal Endometriosis Peritoneal Diseases Animals Animals Calcitonin Gene-Related Peptide Calcitonin Gene-Related Peptide Calcitonin Gene-Related Peptide Cell Transdifferentiation Cell Transdifferentiation Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Epithelial-Mesenchymal Transition Epithelial-Mesenchymal Transition Female

Citation neighborhood (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (51)

Cited by (33)

Source provenance

europepmc
last seen: 2026-10-14T06:08:39.101224+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-10-08T21:23:32.775659+00:00
License: CC0 · commercial use OK