Activated mast cells and nerve fiber proximity in the eutopic endometrium and myometrium of women with endometriosis: a double-immunostaining study

Objective To quantify morphologically degranulating tryptase-positive mast cells (aMCt) and examine their spatial relationship with nerve fibers in the eutopic endometrium, endometrial–myometrial interface, and myometrium of women with endometriosis. Design Cross-sectional histological study of archival specimens using double immunostaining. Setting Academic tertiary pathology service. Patient(s) Hysterectomy specimens from women with surgically and histologically confirmed endometriosis (n = 14). Intervention(s) None. Main outcome measure(s) Densities of aMCt (cells/mm²) and nerve fibers (fibers/mm²), compartment-specific distribution, and the number of aMCt located within the prespecified proximity threshold of nerve trunks. Result(s) aMCt were rare in the functional endometrial layer (< 1 cell/mm²) and sparse and unevenly distributed in the basal layer (11.6 ± 4.7 cells/mm²). The most prominent descriptive finding was a higher aMCt density in the myometrium (88.6 ± 44.0 cells/mm²) than in the sampled endometrial layers. Mean myometrial aMCt densities were descriptively similar in proliferative- and secretory-phase specimens (89.7 ± 16.9 and 87.1 ± 19.1 cells/mm², respectively). Nerve fibers were identified in the basal layer (11.6 ± 4.7 fibers/mm²) but were infrequent in the functional layer (< 0.1 fibers/mm²). In selected specimens, 6–12 aMCt were observed around individual nerve trunks, predominantly in secretory-phase tissue at the endometrial–myometrial interface and within the myometrium. However, most aMCt were distributed independently of neural structures. aMCt were infrequently observed in the available coexisting adenomyosis and fibroid tissue. Conclusion(s) In this small descriptive series, morphologically degranulating tryptase-positive mast cells were more frequently observed in the myometrium than in the sampled endometrial layers. A consistent spatial association between aMCt and nerve fibers was not demonstrated. Occasional proximity, observed mainly in secretory-phase specimens, is hypothesis-generating and should not be interpreted as evidence of temporal regulation, pain generation, or a causal neuroimmune interaction. Larger controlled studies incorporating standardized spatial analyses and clinical pain phenotyping are required. Similar content being viewed by others Abbreviations - aMCT: - Activated mast cells tryptase

I would like to acknowledge the great mentorship I had from the Late Professor IS Fraser. Funding This study was funded by the University of Sydney as part of my PhD. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate The study was approved by the Ethics Review Committee of the Sydney Southwest Area Health Service [Protocol number X05-0345] and the University of Sydney Human Research Ethics Committee [Ref. No. 10761]. All participants provided informed consent. All procedures involving human participants were performed in accordance with the ethical standards of the relevant institutional committees and with the Declaration of Helsinki and its later amendments. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Al-Jefout, M. Activated mast cells and nerve fiber proximity in the eutopic endometrium and myometrium of women with endometriosis: a double-immunostaining study. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04982-2 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04982-2