Mast cell-induced immunopathology in recurrent pregnancy losses.

Abstract

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). Endometrial biopsy was performed 5-7days 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). 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. 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.