Burrowing behavior is a potential non-invasive proxy for lesion development in a syngeneic murine model of endometriosis

Megha Anchan, Megha M Anchan, Samruddhi Deshpande, Atharvaraj Hande, Rooma Sinha, Jayesh Mudgal, Krishnadas Nandakumar, K Nandakumar, Rahul Dutta
BMC women's health · 2025 · vol. 26(1) , pp. 39 · doi:10.1186/s12905-025-04112-4 · PMID:41388524 · PMC12822023 · W4417276029
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study demonstrates that decreased burrowing behavior in mice accurately predicts the presence of endometriosis lesions, offering a non-invasive method for preclinical research.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

This study evaluated whether a non-invasive burrowing assay could predict lesion development in a syngeneic murine model of endometriosis (EM) across three mouse strains (C57BL/6j, BALB/c, and Swiss albino). Using burrowing behavior measured before dissection, EM mice showed reduced burrowing, and recipients were stratified into low and high burrow-score groups; LB mice additionally displayed decreased exploration and increased thermal sensitivity, and post-dissection results showed LB+ animals had ectopic lesions whereas HB animals were lesion-negative. Burrowing performance correlated with lesion presence by ROC analysis (combined AUC 0.883, with AUC 1 in C57BL/6j). A key limitation stated is the need for non-invasive biomarkers because lesion induction in syngeneic models is inconsistent, and the approach still relies on behavioral readouts rather than direct longitudinal lesion imaging. This paper is centrally about endometriosis — developing an ethologically valid burrowing assay as a non-invasive predictor of lesion incidence and progression in a syngeneic mouse EM model.

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Abstract

BACKGROUND: Endometriosis (EM) is a persistent, chronic inflammatory condition associated with excruciating pelvic pain and infertility. The absence of a pre-clinical model that reliably replicates the clinical and functional hallmarks of human EM continues to limit progress in the domain. Furthermore, no rodent model developed to date has achieved a 100% incidence rate, compromising the reproducibility of existing models. Further, the inability to detect lesion development without sacrificing the animal presents a significant barrier for preclinical interventional trials designed to improve the management of EM. METHODS: We employed a non-invasive method based on the altered burrowing behavior of the animal to predict lesion development in the syngeneic mice EM model. We used the burrowing assay (BA) before dissection as a non-invasive behavioral marker to evaluate lesion progression across three distinct laboratory strains: C57BL/6j, BALB/c, and Swiss albino to account for variation due to genetic, immunological, and strain specificity. RESULTS: EM mice displayed a significant decline in burrowing activity compared to controls across all three strains. Based on BA performance, recipient mice were stratified into two groups: Recipients with a low burrow score (LB) and those with a high burrow score (HB). Additionally, LB mice exhibited decreased exploratory behavior and increased sensitivity to thermal pain. In contrast, HB mice had exploratory and thermal responses comparable to those of the control group. Post-dissection, LB mice were presented with ectopic lesions (LB+), whereas HB mice were lesion-negative (HB-). BA performance correlated strongly with lesion presence via ROC analysis, with a combined AUC of 0.883 (and an AUC of 1 for C57BL/6j), indicating excellent diagnostic accuracy of BA in predicting EM incidence. The combined approach of correlating burrowing behavior with other evoked behavioral responses and non-evoked provided a comprehensive assessment of EM disease progression. CONCLUSION: To our knowledge, our research provides evidence for the feasibility of ethologically valid burrowing behaviour as a non-invasive predictor of EM incidence in the syngeneic mice model. Future preclinical drug research for EM management could leverage BA to identify and select only lesion-positive animals for intervention trials. This approach will enhance the translational value of EM research.

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Outcome instruments

VAS-pain

Condition tags

endometriosisinfertility

MeSH descriptors

Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal Behavior, Animal

Citation neighborhood

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.

References (46)

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