recurrent spontaneous abortion
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2022 ◽  
Vol 12 ◽  
Author(s):  
Long Zhao ◽  
Jinhua Fu ◽  
Feng Ding ◽  
Juan Liu ◽  
Lin Li ◽  
...  

Normal pregnancy is related to the successful transition from type 1 cellular immunity to type 2 cellular immunity. Therefore, this study aimed to investigate whether there is abnormal expression of cytokines in the process of inducing Recurrent spontaneous abortion (RSA). Interleukin (IL)-33 is a new member of the IL-1 family, and ST2, as IL-33’s receptor, induced the production of type 2 cytokines. In this study, blood samples were collected from 19 non-pregnant women of normal childbearing age, 28 normal pregnant women, and 33 women with RSA. The serum concentrations of IL-33 and ST2 were detected by flow cytometry. Our results showed that the serum concentrations of IL-33 and ST2 in the RSA group were significantly higher than those in the healthy control group (IL-33: P < 0.05; ST2: P < 0.0001), and IL-33 and ST2 had a higher level in the process of RSA predictive value. In addition, this study initially found that the serum concentrations of IL-33 and ST2 were not significantly correlated with the number of weeks of pregnancy, and there was a lower correlation between IL-33 and ST2 during RSA. This result may be related to the small number of cases. This study is the first time to correlate the changes in serum concentrations of IL-33 and ST2 with RSA, which may be a novel biomarker for the prediction and treatment of RSA.


BIOCELL ◽  
2022 ◽  
Vol 46 (4) ◽  
pp. 1013-1023
Author(s):  
JIABAO WU ◽  
XIAOHUA LIU ◽  
LU HAN ◽  
HUA NIE ◽  
YUAN TANG ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Damin Zhu ◽  
Huijuan Zou ◽  
Jinxian Liu ◽  
Jing Wang ◽  
Cong Ma ◽  
...  

Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.


2021 ◽  
Author(s):  
Mina Badiee ◽  
Mehri Ghafourian ◽  
Ata A. Ghadiri ◽  
Abdolah Mousavi Salehi ◽  
Roshan Nikbakhat ◽  
...  

Abstract BackgroundAppearance of improper immune responses against the fetus and/or inadequate immunoregulatory mechanisms during pregnancy may lead to recurrent spontaneous abortion (RSA). TH17 cells play a significant role in inducing inflammation, autoimmune disease, and acute transplant rejection, while regulatory T (Treg) cells moderate the function of immune system in order to retain homeostasis.MethodsThis case-control study was designed to evaluate TH17 as well as Treg cells in 25 women with RSA and 25 age-matched healthy non-pregnant women. Flow cytometric assay was performed using monoclonal antibodies to detect CD4+CD25+ Treg cells (CD25dim and CD25bright). FoxP3 and RORγt expressions were compared using real-time PCR, and pro-inflammatory and anti-inflammatory cytokines were measured by ELISA kits. Independent-samples T test was employed for statistical analysis. ResultsThe ratio of CD4+CD25bright T cells was remarkably lower in women with RSA (P<0.05), and CD4+CD25dim T cells did not show any significant difference among the groups (P>0.05). RORγt was up-regulated, and FoxP3 was down-regulated significantly in case group (P<0.05). The significant increase of IL-6 and IL-17 as well as the decrease of TGF-β was indicated in RSA group (P<0.05). Also, IL-10 did not vary among the groups (P>0.05). ConclusionThese remarks prove that the decrease in regulatory factors such as CD4+CD25bright T-cells, TGF-β and FoxP3 expression may disrupt immune tolerance and homeostasis during pregnancy. Also, the environment rich in RORγt, IL-6, and IL-17 suggests the detrimental role of TH17 cells, which may lead to fetal rejection.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nana Li ◽  
Nafiseh Saghafi ◽  
Zahra Ghaneifar ◽  
Seyed Abdorahim Rezaee ◽  
Houshang Rafatpanah ◽  
...  

VitD3 may contribute to a successful pregnancy through modulation of immune responses, so VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well.Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on IL-25 and related cytokines of Th17 cells including IL-17A, IL-6, and IL-23 in peripheral blood mononuclear cells of healthy women as a control group and women with unexplained recurrent spontaneous abortion.Method: Isolation of peripheral blood mononuclear cells (PBMCs) was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 h) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, real-time PCR and ELISA were carried out.Results: The proportion of Th17 cells in women with URSA was considerably higher than in the control group. IL-25 mRNA and protein levels in cultured PBMCs from women with URSA were lower than the controls. 1,25VitD3 increased IL-25 expressions at both the protein and mRNA levels in PBMCs from women with URSA relative to the control group. Additionally, 1,25VitD3 treatment not only significantly decreased the percentage of Th17 cells frequency but also reduced expressions of IL-6, IL-17A, and IL-23 in PBMCs from women with URSA.Conclusion: 1,25VitD3 may diminish inflammatory responses cells via downregulation of IL-25 expression. It could be an interesting subject for future researches in the field of the immunopathology of URSA to identify molecular pathways in URSA treatment.


2021 ◽  
Vol 5 (6) ◽  
pp. 20-23
Author(s):  
Jingyi Wang ◽  
Nan Li

This article is a summary of the research progress of the maternal-fetal interface immune microenvironment regulated by traditional Chinese medicine in the treatment of recurrent spontaneous abortion. The imbalance of the immune microenvironment at the maternal-fetal interface is closely related to the occurrence of recurrent spontaneous abortion. Traditional Chinese medicine can maintain the homeostasis of the immune microenvironment at the maternal-fetal interface by regulating the function of immune cells and the expression of related cytokines.


Author(s):  
Ye Shang ◽  
Shujuan Wu ◽  
SaiJiao Li ◽  
Xiaolin Qin ◽  
Jiao Chen ◽  
...  

AbstractMacrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal–fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy‐related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP‐1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yong Huang ◽  
Jiayuan Hao ◽  
Yuan Liao ◽  
Lihua Zhou ◽  
Kaiju Wang ◽  
...  

Abstract Background Recurrent spontaneous abortion (RSA) is one of the common complication of pregnancy, bringing heavy burden to the patients and their families. The study aimed to explore the lncRNA-miRNA-mRNA network associated with recurrent spontaneous abortion. Methods By transcriptome sequencing, we detected differences in lncRNA, miRNA and mRNA expression in villus tissue samples collected from 3 patients with RSA and 3 normal abortion patients. Differentially expressed lncRNAs, miRNAs and genes (DELs, DEMs and DEGs, respectively) were identified, and Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the functions of DELs and DEGs, which were analysed by Fisher’s test. We also observed the regulatory relationships between miRNA-mRNA and lncRNA-miRNA by Cytoscape 3.6.1. Results The results showed that 1008 DELs (523 upregulated and 485 downregulated), 475 DEGs (201 upregulated and 274 downregulated) and 37 DEMs (15 upregulated and 22 downregulated) were identified. And we also constructed a novel lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 genes (NTNG2, GRIA1 and AQP1). Conclusions lncRNA-related ceRNA network containing 31 lncRNAs, 1 miRNA (hsa-miR-210-5p) and 3 mRNAs (NTNG2, GRIA1 and AQP1) was constructed. The results may provide a basic theory for elucidating the mechanism underlying RSA.


2021 ◽  
Author(s):  
Zhuo Chang ◽  
Hai-xue Kuang ◽  
Xueming Zhou ◽  
Hui Zhu ◽  
Yang Zhang ◽  
...  

Abstract Deficient endometrial decidualization has been associated with unexplained recurrent spontaneous abortion (URSA). However, the underlying mechanism is poorly understood. Here, we aimed to investigate the temporal cytokine changes and the involvement of the cyclin D-cyclin-dependent kinase (CDK)4/CDK6 and cyclin E-CDK2 pathways in the regulation of the G1 phase of the cell cycle during decidualization in a murine model of URSA. Serum and decidual tissues of URSA group and normal pregnant (NP) group mice were collected from gestation day 4 (GD4) to GD8. The embryo resorption and abortion rates were observed on GD8 and the decidual tissue status was assessed using hematoxylin and eosin staining. Cytokine levels in decidual tissues were analyzed using western blotting and reverse transcription polymerase chain reaction. We found that the embryo resorption rate was significantly increased in the URSA group compared to that in the NP group on GD8. The expression of the decidualization marker prolactin in the serum and decidual lysate of the URSA group was significantly decreased on GD6-8 compared to that of the NP group. Cyclin D, CDK4, CDK6, cyclin E, CDK2 and pRb levels in the URSA group mice were significantly lower compared to those in the NP group mice on GD6-8. Our results suggest that the hyperactivated cyclin D-CDK4/CDK6 and cyclin E CDK2 pathways inhibit the decidualization process on GD4, leading to deficient decidualization on GD8. Moreover, they clarify the role of cytokines in the cyclin D-CDK4/6 and cyclin E-CDK2 pathways during decidualization and provide new insight into URSA pathogenesis.


2021 ◽  
Author(s):  
Ying Cui ◽  
Li Zou ◽  
Qian Ye ◽  
Dandan Li ◽  
Huiming Wu ◽  
...  

Abstract Objective The changes of microbial community in pregnant women, let alone those of patients with recurrent spontaneous abortion (RSA), remain unclear. We analyzed the differences of gut mircobiota (GM) between RSA patients and pregnant women to find the possible mechanism of RSA. MethodsWe enrolled 30 RSA patients (RSA group) and 30 pregnant women who terminated their pregnancy and did not have a history of spontaneous abortion (NR group) in our hospital from June 2020 to August 2020, and fecal samples were obtained to analyze the GM using 16S rDNA V3–V4 sequencing.ResultsAt the phylum level, we found that there is no significant difference in composition of GM between RSA and NR. But at the genus level, compared with NR, Roseburia significantly decreased (P<0.01), and Ruminococcus significantly increased in RSA patients (P<0.05). Further analysis indicated that Klebsiella (P<0.05) was significantly increased, Prevotella.9 (P<0.05) and Roseburia (P<0.05) were significantly decreased in RSA2 group (BMI>23.9 in RSA). Moreover, Agathobacter (P<0.01) was significantly increased in NR2 group (no delivery in NR). Functional prediction indicated that GM may interfere with RSA through membrane transport, carbohydrate metabolism, amino acid metabolism and other pathways.ConclusionDecreased Roseburia in GM of pregnant women maybe related to RSA. Our results provide the basis for in-depth studies of the composition of gut microbial communities in RSA.


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