Spatial Phenotype of the Mast Cell Population in Endometritis of Various Severities

Sep 30, 2026

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Endometritis features an inflammatory milieu in the endometrium, accompanied by recruitment of immunocompetent cells, including mast cells (MCs). The mechanisms behind MC participation in chronic endometritis (CE) and fibrous niche formation are poorly understood, especially spatial intercellular interactions in situ. Using multiplex immunohistochemistry and quantitative immunofluorescence with AI-assisted analysis, MC distribution spatial phenotype was mapped in CE.

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Article Spatial Phenotype of the Mast Cell Population in Endometritis of Various Severities Sergey Mikhalev 1, Andrey Kostin 2, Mark Kurtser 1, Victor Radzinsky 2, Mekan Orazov 2, Alexander Alekhnovich 2, Aleksandra Prikhodko 2, Grigory Demyashkin 3, Ilya Klabukov 4, Denis Baranovskii 4, Daniel Elieh-Ali-Komi 5,6, Igor Buchwalow 2,7, Markus Tiemann 7, Liudmila Mikhaleva 8 and Dmitrii Atiakshin 2,9, * Academic Editors: Aida Paivandy and Jung-Hye Choi Received: 13 October 2025 Revised: 16 December 2025 Accepted: 22 December 2025 Published: 24 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia; [mikhalev@me.com](mikhalev@me.com) (S.M.); [m.kurtser@mcclinics.ru](m.kurtser@mcclinics.ru) (M.K.) 2 RUDN University, 6 Miklukho-Maklaya St., 117198 Moscow, Russia; [andocrey@mail.ru](andocrey@mail.ru) (A.K.); [radzinsky@mail.ru](radzinsky@mail.ru) (V.R.); [omekan@mail.ru](omekan@mail.ru) (M.O.); [alekhnovich_av@pfur.ru](alekhnovich_av@pfur.ru) (A.A.); [prikhodko_at@pfur.ru](prikhodko_at@pfur.ru) (A.P.); [buchwalow@pathologie-hh.de](buchwalow@pathologie-hh.de) (I.B.) 3 I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St., 8/2, 119048 Moscow, Russia; [dr.dga@mail.ru](dr.dga@mail.ru) 4 National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Koroleva St. 4, 249036 Obninsk, Russia; [doc.baranovsky@gmail.com](doc.baranovsky@gmail.com) (D.B.) 5 Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, 10117 Berlin, Germany; [daniel.elieh-ali-komi@charite.de](daniel.elieh-ali-komi@charite.de) 6 Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, 12203 Berlin, Germany 7 Institute for Hematopathology, Fangdieckstr. 75a, 22547 Hamburg, Germany; [mtiemann@hp-hamburg.de](mtiemann@hp-hamburg.de) [8](8 Scientific Research Institute of Human Morphology Named After Academician A.P)[ Scientific Research Institute of Human Morphology Named After Academician A.P](8 Scientific Research Institute of Human Morphology Named After Academician A.P). Avtsyn, Russian Scientific Center of Surgery Named after Academician B.V. Petrovsky, 127051 Moscow, Russia; [mikhalevalm@yandex.ru](mikhalevalm@yandex.ru) 9 Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia * Correspondence: atyakshin-da@rudn.ru Abstract Endometritis features an inflammatory milieu in the endometrium, accompanied by the recruitment of immunocompetent cells, including mast cells (MCs) . The mechanisms underlying MC involvement in chronic endometritis (CE) and fibrous niche formation remain poorly understood, particularly regarding spatial intercellular interactions in situ. In this study, we used multiplex immunohistochemistry and quantitative immunofluorescence analysis to map the spatial phenotype of MC distribution. Standard histochemical techniques, monoplex and multiplex immunohistochemical staining technologies, light-field microscopy, epifluorescence, and confocal microscopy with multispectral imaging, combined with quantitative immunofluorescence analysis with AI application, were used to identify the spatial phenotyping of quantitative and qualitative features of the endometrial MC population in CE. The increased intensity of endometrial inflammation was accompanied by a rise in the profile of MC content in the endometrium; this accounted for a 0.014% increase in the control and 0.067%, 0.113%, and 0.206% increases in mild, moderate, and severe CE, respectively. We are the first to map the number of MCs that demonstrated loci

FAQs

What is the main research focus of this study?

It maps the spatial phenotype of mast cell distribution in chronic endometritis and characterizes how mast cells interact with other immune cells in situ.

Which methods were used to study mast cell spatial distribution?

Multiplex immunohistochemistry and quantitative immunofluorescence analysis were used, supported by light-field, epifluorescence, and confocal microscopy with multispectral imaging and AI-assisted quantification.

How does mast cell spatial behavior relate to disease severity?

Increasing endometrial inflammation was associated with a higher profile of MC content and with loci of mast-cell accumulations that correlate with the severity of chronic endometritis and clinical signs.

Sep 30, 2026

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