Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology

Alison McCallion, Yasmin Nasirzadeh, Chandrakant Tayade, Mallikarjun Bidarimath, Danielle J Sisnett, Harshavardhan Lingegowda, Soohyun Ahn, Bruce A. Lessey, Madhuri Koti, Stephany P. Monsanto, Steven L. Young, Andrew W. Craig, Kasra Khalaj, Jessica E. Miller
2022 · doi:10.17615/me81-9148 · W4294368727
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

This study found that endometriotic lesions recruit and differentiate mast cells through estrogen-mediated pathways, contributing to inflammation and disease progression.

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This study examined how estrogen may regulate mast cells within endometriotic lesions by comparing endometriotic tissue to matched eutopic endometrium from the same patients. The authors found increased mast cell numbers in endometriotic lesions along with higher stem cell factor (SCF) levels, and they reported an endometriotic microenvironment with upregulated mast-cell–recruiting/differentiating genes (including CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG). In vitro, endometriotic epithelial and endometrial stromal cells exposed to mast cell–conditioned media produced more pro-inflammatory and chemokinetic cytokines, and in an estrogen-treated mouse model, mature mast cells increased in peritoneal fluid and mast-cell–relevant genes and Alcian blue–stained mast cell density were higher in estrogen-treated endometriotic lesions. The paper explicitly frames these findings as supporting a mechanistic link but does not provide patient-level functional outcomes tying mast cell activity to symptom severity. This paper is centrally about endometriosis — it investigates estrogen-driven mast cell recruitment and inflammatory signaling in endometriotic lesions.

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Abstract

Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression.
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Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology Public DepositedAdd to collection You do not have access to any existing collections. You may create a new collection. Downloadable Content Download PDFCitation MLA Mc Callion, Alison, et al. Estrogen Mediates Inflammatory Role of Mast Cells In Endometriosis Pathophysiology. 2022. https://doi.org/10.17615/me81-9148APA Mc Callion, A., Nasirzadeh, Y., Lingegowda, H., Miller, J., Khalaj, K., Ahn, S., Monsanto, S., Bidarimath, M., Sisnett, D., Craig, A., Young, S., Lessey, B., Koti, M., & Tayade, C. (2022). Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology. https://doi.org/10.17615/me81-9148Chicago Mc Callion, Alison, Yasmin Nasirzadeh, Harshavardhan Lingegowda, Jessica E Miller, Kasra Khalaj, Soo Hyun Ahn, Stephany P Monsanto et al. 2022. Estrogen Mediates Inflammatory Role of Mast Cells In Endometriosis Pathophysiology. https://doi.org/10.17615/me81-9148- Creator - McCallion, Alison - Other Affiliation: Queen's University - Nasirzadeh, Yasmin - Other Affiliation: Queen's University - Lingegowda, Harshavardhan - Other Affiliation: Queen's University - Miller, Jessica E. - Other Affiliation: Queen's University - Khalaj, Kasra - Other Affiliation: Queen's University - Ahn, SooHyun - Other Affiliation: Queen's University - Monsanto, Stephany P. - Other Affiliation: Queen's University - Bidarimath, Mallikarjun - Other Affiliation: Queen's University - Sisnett, Danielle J. - Other Affiliation: Queen's University - Craig, Andrew W. - Other Affiliation: Queen's University - Young, Steven L. - School of Medicine, Department of Obstetrics and Gynecology - Lessey, Bruce A. - Other Affiliation: Wake Forest Baptist Health - Koti, Madhuri - Other Affiliation: Queen's University - Tayade, Chandrakant - Other Affiliation: Queen's University - McCallion, Alison - Abstract - Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression. - Date of publication - 2022 - DOI - Identifier - Resource type - Article - Rights statement - In Copyright - License - Attribution 4.0 International - Journal title - Frontiers in Immunology - Journal volume - 13 - Language - English - Version - Publisher - ISSN - 1664-3224 Relations - Parents: - In Collection: This work has no parents. Items | Thumbnail | Title | Date Uploaded | Visibility | Actions | |---|---|---|---|---| | fimmu-13-961599.pdf | 2022-09-02 | Public | Download |

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