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Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health

Oliver Richards Orcid Logo, Megan Cotterell, Cathy Thornton Orcid Logo, April Rees Orcid Logo

ImmunoHorizons, Volume: 10, Issue: 3

Swansea University Authors: Oliver Richards Orcid Logo, Cathy Thornton Orcid Logo, April Rees Orcid Logo

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DOI (Published version): 10.1093/immhor/vlag013

Abstract

Reproductive disorders such as endometriosis and polycystic ovary syndrome (PCOS) are increasingly recognized as immune-mediated conditions, yet their immunopathology remains poorly understood. Menstrual blood, a noninvasive and biologically relevant sample, offers a unique window into reproductive...

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Published in: ImmunoHorizons
ISSN: 2573-7732
Published: Oxford University Press (OUP) 2026
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URI: https://cronfa.swan.ac.uk/Record/cronfa71598
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Menstrual blood, a noninvasive and biologically relevant sample, offers a unique window into reproductive tract immunity but has been underutilized in this context. We optimized Cytek&#x2019;s&#xAE; 25-color high-dimensional flow cytometry panel by incorporating a mitochondrial dye to investigate immune cell profiles in menstrual mononuclear cells (MMCs) from healthy individuals, and those with endometriosis or PCOS, in comparison with matched peripheral blood mononuclear cells (PBMCs). This enabled detailed assessment of 40 immune cell subsets and 546 immunological parameters, including markers of activation, exhaustion, migration, and mitochondrial content. MMCs displayed a distinct immune landscape compared to PBMCs, enriched with tissue-resident NK cells, macrophages, and dendritic cells, alongside changes in mitochondrial mass for various cell subsets and other markers such as PD-1. These findings support a metabolically active, tissue-adapted immune environment within menstrual fluid, representative of the reproductive tract. Exploratory analyses of MMCs from individuals with endometriosis or PCOS revealed disease-specific trends: for example, mitochondrial mass differed across Tregs, CD4 central memory cells, plasmablasts, and cDC1s, with endometriosis and PCOS exhibiting distinct patterns rather than a uniform &#x201C;reproductive disorder&#x201D; phenotype. Although these disease-associated findings did not consistently reach statistical significance due to the small cohort size, they demonstrate the potential of menstrual blood immunoprofiling to uncover biologically meaningful differences across diverse immune cell populations. 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spelling 2026-04-28T11:17:20.4415016 v2 71598 2026-03-09 Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health 93c672d7c4bf8ebe19916d432f0ec7bb 0000-0002-5824-2745 Oliver Richards Oliver Richards true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false ae088f7f8609d2b2ea4666f9b52b3c15 0000-0002-4408-634X April Rees April Rees true false 2026-03-09 MEDS Reproductive disorders such as endometriosis and polycystic ovary syndrome (PCOS) are increasingly recognized as immune-mediated conditions, yet their immunopathology remains poorly understood. Menstrual blood, a noninvasive and biologically relevant sample, offers a unique window into reproductive tract immunity but has been underutilized in this context. We optimized Cytek’s® 25-color high-dimensional flow cytometry panel by incorporating a mitochondrial dye to investigate immune cell profiles in menstrual mononuclear cells (MMCs) from healthy individuals, and those with endometriosis or PCOS, in comparison with matched peripheral blood mononuclear cells (PBMCs). This enabled detailed assessment of 40 immune cell subsets and 546 immunological parameters, including markers of activation, exhaustion, migration, and mitochondrial content. MMCs displayed a distinct immune landscape compared to PBMCs, enriched with tissue-resident NK cells, macrophages, and dendritic cells, alongside changes in mitochondrial mass for various cell subsets and other markers such as PD-1. These findings support a metabolically active, tissue-adapted immune environment within menstrual fluid, representative of the reproductive tract. Exploratory analyses of MMCs from individuals with endometriosis or PCOS revealed disease-specific trends: for example, mitochondrial mass differed across Tregs, CD4 central memory cells, plasmablasts, and cDC1s, with endometriosis and PCOS exhibiting distinct patterns rather than a uniform “reproductive disorder” phenotype. Although these disease-associated findings did not consistently reach statistical significance due to the small cohort size, they demonstrate the potential of menstrual blood immunoprofiling to uncover biologically meaningful differences across diverse immune cell populations. Together, this study establishes menstrual fluid as a valuable, non-invasive sample for immunological assessment and a promising avenue for future biomarker discovery in reproductive disorders. Journal Article ImmunoHorizons 10 3 Oxford University Press (OUP) 2573-7732 endometriosis, immune cells, menstrual blood, PCOS, reproduction 25 3 2026 2026-03-25 10.1093/immhor/vlag013 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) Royal Society (RGS\"R2\"242264) 2026-04-28T11:17:20.4415016 2026-03-09T11:36:24.0216199 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Oliver Richards 0000-0002-5824-2745 1 Megan Cotterell 2 Cathy Thornton 0000-0002-5153-573X 3 April Rees 0000-0002-4408-634X 4 71598__36621__8013ec966c9047208f7e4dbc1eb9356b.pdf 71598.VoR.pdf 2026-04-28T11:15:18.9581358 Output 1761913 application/pdf Version of Record true © The Author(s) 2026. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. true eng https://creativecommons.org/licenses/by/4.0/)
title Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
spellingShingle Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
Oliver Richards
Cathy Thornton
April Rees
title_short Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
title_full Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
title_fullStr Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
title_full_unstemmed Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
title_sort Revealing the immune landscape of menstrual blood: unlocking insights into activation, exhaustion, and mitochondrial mass for reproductive health
author_id_str_mv 93c672d7c4bf8ebe19916d432f0ec7bb
c71a7a4be7361094d046d312202bce0c
ae088f7f8609d2b2ea4666f9b52b3c15
author_id_fullname_str_mv 93c672d7c4bf8ebe19916d432f0ec7bb_***_Oliver Richards
c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
ae088f7f8609d2b2ea4666f9b52b3c15_***_April Rees
author Oliver Richards
Cathy Thornton
April Rees
author2 Oliver Richards
Megan Cotterell
Cathy Thornton
April Rees
format Journal article
container_title ImmunoHorizons
container_volume 10
container_issue 3
publishDate 2026
institution Swansea University
issn 2573-7732
doi_str_mv 10.1093/immhor/vlag013
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Reproductive disorders such as endometriosis and polycystic ovary syndrome (PCOS) are increasingly recognized as immune-mediated conditions, yet their immunopathology remains poorly understood. Menstrual blood, a noninvasive and biologically relevant sample, offers a unique window into reproductive tract immunity but has been underutilized in this context. We optimized Cytek’s® 25-color high-dimensional flow cytometry panel by incorporating a mitochondrial dye to investigate immune cell profiles in menstrual mononuclear cells (MMCs) from healthy individuals, and those with endometriosis or PCOS, in comparison with matched peripheral blood mononuclear cells (PBMCs). This enabled detailed assessment of 40 immune cell subsets and 546 immunological parameters, including markers of activation, exhaustion, migration, and mitochondrial content. MMCs displayed a distinct immune landscape compared to PBMCs, enriched with tissue-resident NK cells, macrophages, and dendritic cells, alongside changes in mitochondrial mass for various cell subsets and other markers such as PD-1. These findings support a metabolically active, tissue-adapted immune environment within menstrual fluid, representative of the reproductive tract. Exploratory analyses of MMCs from individuals with endometriosis or PCOS revealed disease-specific trends: for example, mitochondrial mass differed across Tregs, CD4 central memory cells, plasmablasts, and cDC1s, with endometriosis and PCOS exhibiting distinct patterns rather than a uniform “reproductive disorder” phenotype. Although these disease-associated findings did not consistently reach statistical significance due to the small cohort size, they demonstrate the potential of menstrual blood immunoprofiling to uncover biologically meaningful differences across diverse immune cell populations. Together, this study establishes menstrual fluid as a valuable, non-invasive sample for immunological assessment and a promising avenue for future biomarker discovery in reproductive disorders.
published_date 2026-03-25T07:37:33Z
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