Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.

McCallion, Alison

Nasirzadeh, Yasmin

Lingegowda, Harshavardhan

Miller, Jessica E

Khalaj, Kasra

Ahn, SooHyun

Monsanto, Stephany P

Bidarimath, Mallikarjun

Sisnett, Danielle J

Craig, Andrew W

Young, Steven L

Lessey, Bruce A

Koti, Madhuri

Tayade, Chandrakant

2023-10-01T15:12:40Z

2023-10-01T15:12:40Z

2022-01

2023-10-01T15:12:37Z

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.

1664-3224

1664-3224

https://hdl.handle.net/10161/29057

eng

Frontiers Media SA

Frontiers in immunology

10.3389/fimmu.2022.961599

Mast Cells

Animals

Mice, Inbred C57BL

Humans

Mice

Endometriosis

Estrogens

Cell Count

Female

Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.

Journal article

Young, Steven L|0000-0002-5205-4495

961599

Duke

School of Medicine

Clinical Science Departments

Obstetrics and Gynecology

Obstetrics and Gynecology, Reproductive Endocrinology & Fertility

Published

13