Increased uNK cells in mid-secretory endometrium are associated with increased vascularization and defective vascular transformation of spiral arteries in women with RPL.
Problem: Does programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) expression on the T-cell subsets such as T helper (Th) 1, Th17, and Treg cells differentiate women with recurrent pregnancy losses (RPL) from normal fertile women?
Method of study:The study was designed as a prospective cohort study. Forty-five women with two or more RPL of unknown etiology and twenty fertile women who had at least one or more live-born infants were enrolled prospectively from Jan 2017 to Jul 2019. PD-1 and PD-L1 expression on T-cell subsets were measured by flow cytometric analysis.
Results:The proportions of PD-1 + Th1 (CD4 + /IFN-γ + /CD279 + and CD4 + /TNF-α + / CD279 + ) and PD-1 + Th17 cells (CD4 + /IL17 + /CD279 + ) were significantly lower in RPL group than those of controls (P < .05, respectively). The proportion of PD-1 + Tregs (CD4 + /CD25 + /CD127 dim/− /CD279 + ) in RPL group was not different from that of controls. The proportion of PD-L1 + Th17 cells (CD4 + IL17 + CD274 + ) was significantly lower as compared with that of /controls (P < .05). However, the proportions of PD-L1 + Th1 (CD4 + /IFN-γ + /CD274 + and CD4 + /TNF-α + /CD274 + ) and PD-L1 + Treg (CD4 + / CD25 + /CD127 dim/− /CD274 + ) cells were not different between the RPL group and controls (P > .05, respectively). In Th1, Th17 and Treg cells, the proportions of PD-L1 + (CD274 + ) cells were significantly higher than those of PD-1 + (CD279 + ) cells in both RPL group and controls (P < .05, respectively).
Conclusion: PD-1 and PD-L1 expressions on Th17 cells as well as PD-1 expression onTh1 cells were significantly downregulated in women with RPL, which may lead to increased Th1 and Th17 immunity, and imbalance between Th17, Th1, and Treg cells in women with RPL.
GnRH analogues induce pro-inflammatory TH1 shift in T-cell immunity, in vitro. GnRH treatment during assisted reproductive technology cycle might explain a possible cause of inflammatory flare in women with inflammatory conditions.
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.
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