Dataset Information

The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.

ABSTRACT: Recurrent pregnancy loss (RPL) is a common fertility problem that affects 1%-2% of couples all over the world. Despite exciting discoveries regarding the important roles of the decidual natural killer cell (dNK) and regulatory T cell in pregnancy, the immune heterogeneity in patients with unexplained recurrent pregnancy loss (URPL) remains elusive. Here, we profiled the transcriptomes of 13,953 CD45⁺ cells from three normal and three URPL deciduas. Based on our data, the cellular composition revealed three major populations of immune cells including dNK cell, T cell, and macrophage, and four minor populations including monocytes, dendritic cell (DC), mast cell, and B cell. Especially, we identified a subpopulation of CSF1+ CD59+ KIRs-expressing dNK cells in normal deciduas, while the proportion of this subpopulation was decreased in URPL deciduas. We also identified a small subpopulation of activated dDCs that were accumulated mainly in URPL deciduas. Furthermore, our data revealed that in decidua at early pregnancy, CD8⁺ T cells exhibited cytotoxic properties. The decidual macrophages expressed high levels of both M1 and M2 feature genes, which made them unique to the conventional M1/M2 classification. Our single-cell data revealed the immune heterogeneity in decidua and the potentially pathogenic immune variations in URPL.

SUBMITTER: Chen P

PROVIDER: S-EPMC8218877 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.

Chen Pengfei P Zhou Liying L Chen Jiying J Lu Ying Y Cao Chaoxia C Lv Shuangli S Wei Zhihong Z Wang Liping L Chen Jiao J Hu Xinglin X Wu Zijing Z Zhou Xiaohua X Su Danna D Deng Xuefeng X Zeng Changchun C Wang Huiyun H Pu Zuhui Z Diao Ruiying R Mou Lisha L

Frontiers in immunology 20210607

Recurrent pregnancy loss (RPL) is a common fertility problem that affects 1%-2% of couples all over the world. Despite exciting discoveries regarding the important roles of the decidual natural killer cell (dNK) and regulatory T cell in pregnancy, the immune heterogeneity in patients with unexplained recurrent pregnancy loss (URPL) remains elusive. Here, we profiled the transcriptomes of 13,953 CD45<sup>+</sup> cells from three normal and three URPL deciduas. Based on our data, the cellular comp ...[more]

PMID: 34168655

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Project description:BackgroundUnexplained recurrent pregnancy loss (URPL) is a significant obstetric challenge affecting maternal health and well-being. Genetic factors, including mutations in the methylenetetrahydrofolate reductase (MTHFR) gene and elevated homocysteine levels, are increasingly recognized as contributors to URPL, though their precise roles remain complex. This study aimed to comprehensively explore these factors.ObjectivesThis study examines the links between MTHFR gene polymorphisms (C677T and A1298C), plasma homocysteine levels, and URPL. It also aims to create a predictive model for URPL based on these factors.DesignA case-control study with Vietnamese women who had at least one pregnancy between January 2017 and June 2020, recruited from Medlatec Hospital and Hanoi Medical University. Participants included URPL cases (n = 128) and controls (n = 126).MethodsParticipants were selected based on specific criteria. Main analyses identified the optimal multivariable logistic regression model for predicting URPL using Bayesian Model Averaging, with the optimal model chosen based on the highest Area Under the Curve (AUC) and posterior probability. A nomogram for clinical risk prediction was developed based on parameters from the optimal model.ResultsURPL cases exhibited significantly higher plasma homocysteine levels (11.73 ± 6.08 µmol/L) compared to controls (7.64 ± 1.78 µmol/L), correlating with increased URPL risk (OR: 1.64, 95% confidence interval (CI): 1.41-1.96; p < 0.001). The MTHFR C677T variant showed strong associations with URPL, particularly the CT genotype (OR: 6.07, 95% CI: 3.00-12.93; p < 0.001) and TT genotype (OR: 14.62, 95% CI: 2.85-114.77; p = 0.003). Similarly, the A1298C variant demonstrated elevated URPL risk with the AC genotype (OR: 2.73, 95% CI: 1.34-5.78; p = 0.007) and CC genotype (OR: 12.43, 95% CI: 3.17-64.22; p = 0.001).ConclusionThis study provides insights into the complex interplay of MTHFR gene mutations, elevated homocysteine levels, and URPL. Genetic testing and biomarker assessment may play a crucial role in customizing risk assessment and management strategies for women at risk of URPL.

Project description:Background and aimThe Th17/Treg balance in peripheral blood and reproductive tissues may have a role in the etiology of unexplained recurrent pregnancy loss (URPL). In this study, we evaluated the major cytokine of Treg cells transforming growth factor-beta (TGF-β), and their specific transcription factor Forkhead box P3 (FOXP3), as well as the most highlighted cytokine of Th17 cells (interleukin [IL]-17A) in both URPL patients and healthy women.MethodsSamples were extracted from the peripheral blood, endocervix, endometrium, and vagina of 14 patients with URPL and 12 normal non-pregnant women as a control (normal) group. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines in the serum and cervicovaginal fluid.ResultsWe found that in the URPL group, FOXP3 gene expression was considerably higher in peripheral blood than in the normal group (P=0.043). TGF-β levels in the cervicovaginal fluid were different in the URPL and normal groups (P=0.015). In comparison to the control group, women with URPL had significantly greater IL-17 gene expression in the peripheral blood (P=0.01).ConclusionLower TGF-β levels in the cervicovaginal fluid of patients compared to controls may be related with increased IL-17 and FOXP3 mRNA levels in patients with URPL. Dysregulation of local immune responses in reproductive tissues may represent dysregulation of systemic regulatory immunological responses in the pathogenesis of URPL.Relevance for patientsDysregulation of immune responses may play a role in the pathogenesis of URPL at least in some patients with URPL. We conclude that the breakdown of tolerance in the local immune responses is more critical than the breakdown of tolerance in systemic tolerance in the pathogenesis of URPL. Therefore, modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. The impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies. Therefore, we suggest that transvaginal TGF-β in women with URPL may induce maternal tolerance which leads to the successful pregnancy.

Dataset Information

The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.

Publications

The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.

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