WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Heterologous): heterologous rodent models

M Louise Hull, Raul Gomez, Warren B Nothnick, Katherine A Burns, M. Zahied Johan, Mohammed Zahied Johan, Ingmar Land, Isabella R Land, Stacey A Missmer, Lone Hummelshoj, Kaylon L Bruner-Tran, for the EPHect Experimental Models Working Group, EPHect Experimental Models Working Group, Nick Andrews, Michael S. Anglesio, Caroline B. Appleyard, Joe A. Arosh, Christian M. Becker, Kaylon L. Bruner‐Tran, Ronald L. Chandler, Julie A. Christianson, Fiona L. Cousins, Kelsi N. Dodds, Victor Fattori, Asgi Fazleabas, Caroline E. Gargett, Juan S. Gnecco, Raúl Gómez, Martin Götte, Erin Greaves, Linda G. Griffith, Patrick G. Groothuis, Ruth Grümmer, Sun‐Wei Guo, Shannon M. Hawkins, Lone Hummelshøj, Mark R. Hutchinson, Mohamed Gamal Ibrahim, Elizabeth E. Marr, Stacy L. McAllister, Jeffrey Mogill, Jens Nagel, Paulina Nuñez‐Badinez, Kevin G. Osteen, Daniëlle Peterse, Michael S. Rogers, Andrea Romano, Philippa T. K. Saunders, Miguel Á. Tejada, Kathy L. Sharpe-Timms, Waldiceu A. Verri, Paola Viganò, Katy Vincent
Molecular human reproduction · 2025 · vol. 31(3) · doi:10.1093/molehr/gaaf022 · PMID:40628402 · W4412134313
article OA: hybrid CC0 ⤵ 3 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This paper identifies nine critical variables for heterologous rodent models of endometriosis and provides recommendations for harmonizing experimental approaches to improve reproducibility and comparability of research findings.

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Abstract

Endometriosis, defined as the growth of endometrial-like tissues outside the uterus, is a common disease among women. Numerous in vivo rodent models of endometriosis have been developed to explore multiple aspects of this poorly understood disease. Heterologous models utilize human endometrial tissues engrafted into immunocompromized mice, while homologous models engraft rodent endometrium into immunocompetent mice or rats. Heterologous models of endometriosis more closely replicate the human disease; however, the murine humoral immune response must be suppressed to prevent rejection of the xenograft tissue. Although the innate immune system remains intact, suppression of the humoral response leads to a markedly different local and systemic immune environments compared to humans. Despite this limitation, experiments using heterologous models have contributed significantly to our understanding of endometriosis establishment and progression, the pre-clinical effectiveness of various therapeutic strategies, and genetically modifiable host factors that contribute to disease. Unfortunately, a lack of harmonization of the models used by different laboratories has impeded the reproducibility and comparability of results between groups. Therefore, the World Endometriosis Research Foundation (WERF) formed an international working group of experts in heterologous models of endometriosis to develop guidelines and protocols that could contribute to unifying experimental approaches across laboratories. Nine critical variables were identified: (i) mouse strain; (ii) human tissue type; (iii) hormonal status of the human tissue donor; (iv) human tissue preparation; (v) method and location of tissue placement; (vi) hormonal status of the recipient animal; (vii) whether or not mice were engrafted with human immune cells; (viii) endpoint assessments; and (ix) number and type of replicates. Herein, we outline important considerations for each major variable and make recommendations for unification of approaches. Widespread adoption of harmonized protocols and implementation of standardized documentation and reporting should further improve the reproducibility and translation of experimental findings both within and between laboratories.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks Biological Specimen Banks 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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