Mast cell–induced immunopathology in recurrent pregnancy losses

Abstract

Problem Mast cells (MC) have been known to play an important role in inflammation and angiogenesis by secreting numerous mediators, such as proteases, gelatinases, and proteoglycans. Three different MC subtypes were found in the endometrial layers of the uterus. In this study, we aim to investigate the role of endometrial MCs in recurrent pregnancy losses (RPL). Method of study Endometrial biopsy was performed 5‐7 days post‐ovulation (implantation window) in women with a history of two or more RPL (n = 46) and normal fertile women (n = 10). Quantitative RT‐PCR was performed to detect the expression of various mast cell mediators. Endometrial samples were evaluated using immunohistochemistry for c‐kit receptor (CD117) and tryptase (MC activation marker). Results Mast cells were present throughout the entire layers of the endometrium; their count was elevated in RPL patients as compared to controls. The gene expression of c‐Kit receptor was not different between the study groups. There are significant increases in the mRNA expression of various mediators, that is, stem cell factor (P = 0.029), tryptase (P = 0.024), heparan sulfate (P = 0.0005), and MMP‐2 (P < 0.0001) in women with RPL as compared to normal controls. Chymase gene expression was not detected in most of the endometrial samples. Conclusion This study has shown that MCs are overactive in RPL patients by creating a pro‐inflammatory milieu, suggesting a novel role in the immunopathology of RPL. Future studies are needed to better understand the role of MC in implantation and placental angiogenesis.

Immune Cells in the Uterine Remodeling: Are They the Target of Endocrine Disrupting Chemicals?

“…We anticipate that future studies will contribute to an increasing understanding of the role of single MC mediators for pregnancy success. It is suggested that increased numbers or exacerbated activation of MCs is associated with human pregnancy pathologies like recurrent pregnancy losses (122) and PE (123,124). The mechanisms underlying this phenomenon are not explored.…”

Significance of mast cells in spermatogenesis, implantation, pregnancy, and abortion: Cross talk and molecular mechanisms

“…MCs are found in the endometrium as round or ovoid granular cells more often, whereas elongated shapes of them abound in the basal layer and endometrium/myometrium junction . Leo et al investigated the subtypes of MCs during stages of the menstrual cycle.…”

“…Accumulation of MCs throughout all layers of the endometrium has been reported in women with a history of pregnancy loss. MC activation in these women resulted in higher levels of SCF, tryptase, heparin sulfate, and MMP‐2 . To elucidate the role of MCs in abortion, Woidack et al decided to perform the adoptive transfer of Tregs to support the MC‐mediated angiogenesis in abortion‐prone mice which have lower MC numbers in their uterus tissue.…”

“…It is reported that infertile females have decreased numbers of decidual MCs and lower expression of KIR2DL4 . Interestingly, the presence of MCs throughout the endometrium layers and producing pro‐inflammatory mediators have been reported to contribute to the recurrent pregnancy losses …”

Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes

“…Mast cells are resident immunological cells found abundantly in tissues such as skin, endometrium and placenta that have prominent roles in immunologic reactions [10][11][12][13]. Their presence and prevalence in these tissues, along with their proximity to blood vessels, predispose these cells to be among the first immune cells that can be infected by ZIKV after a mosquito bite penetrates the skin.…”