scholarly journals Microbiota in Uterine Cavity of Unexplained Recurrent Spontaneous Abortion (URSA) Patients in Early Pregnancy

Author(s):  
Shiyu Bai ◽  
Shuai Fu ◽  
Liqiong Zhu ◽  
Manqi Chen ◽  
Bingqian Huang ◽  
...  

Abstract Purpose The purpose of this study is to determine the uterine cavity microbial composition in unexplained recurrent spontaneous abortion (URSA) patients and to understand the correlation between URSA and uterine cavity microbiota. Methods Using the double-lumen embryo transfer tubes to collect uterine cavity fluid samples from pregnant women in their first trimester. 16S rRNA sequencing was conducted to analysis the composition and abundance of the microbiota in samples. Results We enrolled 10 URSA cases and 28 induced miscarriage cases in their early pregnancy. Microbial communities were detected in all samples of URSA group (100%, n = 10) vs. none of control group (0%, n=28). Two most dominant microbes are Lactobacillus and Curvibacter. Conclusion This study showed Lactobacillus and Curvibacter dominated colonizing in uterine cavity of URSA patients during early pregnancy and associated with URSA. Changes of dominant microbiota will lead to bad pregnancy outcome.

2017 ◽  
Vol 29 (8) ◽  
pp. 1613 ◽  
Author(s):  
Liang Xu ◽  
Tian Qiu ◽  
Yudong Wang ◽  
Yan Chen ◽  
Weiwei Cheng

In the present study, the mechanisms underlying the pathogenesis of unexplained recurrent spontaneous abortion (URSA) were explored. The protein and mRNA expression of two C-type lectin-like receptors (CLRs), namely dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and mannose receptor (MR), and two Toll-like receptors (TLRs), namely TLR2 and TLR4, in the decidua and dendritic cells (DCs) was compared between URSA patients and normal controls. URSA patients had significantly lower protein and mRNA expression of DC-SIGN and significantly higher expression of TLR2 and TLR4 in decidual tissues compared with normal controls. In addition, URSA patients had significantly higher levels of the T helper (Th) 1 cytokines interleukin (IL)-2 and interferon-γ, and significantly lower levels of the Th2 cytokines IL-10 and transforming growth factor β1 in decidual tissues compared with the control group. The TLR2 agonist synthetic triacylated lipoprotein (Pam3CSK4) and the TLR4 agonist lipopolysaccharide were used to demonstrate that TLR2 and TLR4 modulate Th1/Th2 cytokine imbalance in DC–T cell cocultures. The results suggest that the balance between CLRs and TLRs was tilted towards a TLR-dominant response in URSA patients, which may disrupt maternal–fetal immune tolerance, resulting in spontaneous abortion.


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 12 ◽  
Author(s):  
Heng Gu ◽  
Longyu Li ◽  
Mengxuan Du ◽  
Hang Xu ◽  
Mengge Gao ◽  
...  

Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA, and ITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs, IFNG may play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.


2009 ◽  
Vol 18 (3) ◽  
pp. 240-247 ◽  
Author(s):  
Giovanni Santone ◽  
Gianmatteo Ricchi ◽  
David Rocchetti ◽  
Stefania Tofani ◽  
Cesario Bellantuono

SUMMARYAim– To review studies conducted to establish the risk of spontaneous abortion (SA) in women exposed to anti-depressant drugs (ADs) during early pregnancy.Methods– By using different search terms, PubMed, Toxline, EMBASE, PsychINFO, and the Cochrane library databases were searched from January 1980 to March 2008, to identify studies assessing the risk of SA in women exposed to different classes of ADs during the first trimester of pregnancy.Results– Ten studies over 21 identified were selected for the analysis. All were performed prospectively and included as control group unexposed women, or exposed to non-teratogenic drugs or to placebo. In seven studies a depressive episode was specified as the reason for which the drug was prescribed, while the time of exposure was in nine.Conclusions– Only three studies over ten selected reported a significant association between an increased rate of SAs and early pregnancy exposure to some ADs. Many methodological flaws in the study design were found in all studies considered. Given this background and a lack of strong evidence on this issue, further prospective and better designed studies are needed to assess the risk of SA in pregnant women exposed to ADs against the risk of an untreated maternal depression.Declaration of Interest:None.


2021 ◽  
Vol 14 ◽  
Author(s):  
Jiefan Gao ◽  
Li Wang ◽  
Lei Bu ◽  
Yangyang Song ◽  
Xiao Huang ◽  
...  

Background: 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 regulatory T cells /Th17 axis, the gene expressions and concentrations of related cytokines including, TGF-β, IL-10, IL-6, IL-23, and IL-17A in peripheral blood mononuclear cells [PBMCs] of healthy women as a control group and women with URSA. Method: Isolation of 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 hours] 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 regulatory T cells was markedly lower, while the proportion of Th17 cells in women with URSA was considerably higher than in the control group [P=0.01, P=0.01]. The ratio of the frequency of Tregs to the baseline [1,25VitD3/Untreated] increased, while the ratio of the frequency of Th17 cells to the baseline decreased in women with URSA relative to the controls [P= 0.01, P=0.04]. 1,25VitD3 increased IL-10 expressions at both the protein and mRNA levels in PBMCs in women with URSA relative to the control group [P=0.0001, P=0.04]. TGF-β levels in the cultured supernatants decreased significantly in the case group in the presence of 1,25VitD3 relative to the controls [P=0.03]. 1,25VitD3 treatment also significantly decreased gene expressions of IL-6, IL-17A, and IL-23 in PBMCs of women with URSA [P=0.01, P=0.001, P=0.0005], as well as the levels of those cytokines in cell culture supernatants [P=0.03, P=0.02, P=0.01, respectively] in women with URSA relative to the controls. Conclusion: According to the findings of this research, modulation of immune responses by 1,25VitD3 is accomplished by strengthening Tregs function and inhibiting inflammatory responses of Th17 cells which may have a positive impact on pregnancy outcome. Thus, as an immunomodulating agent, VitD3 may be effective in reducing the risk of URSA.


2020 ◽  
Vol 7 (10) ◽  
pp. 71-77
Author(s):  
MOHAMED S. A. EMARAH ◽  
MOHAMED A. EL-NAGGAR ◽  
ABEER EL SHABACY ◽  
SAHAR H. QUSHWA

Recurrent miscarriage, defined as loss of two or more consecutive pregnancies, occurs in 1–2% of couples attempting to bear children. The major causes of recurrent pregnancy loss (RPL) based on the literature include parental structural chromosome rearrangement, immunologic factors (i.e. antiphospholipid syndrome), thrombophilic factors (both inherited and acquired), anatomic factors of uterine anomalies, and endocrinologic disorders. Luteal phase defect, polycystic ovarian syndrome (PCOS), diabetes mellitus, thyroid disease and hyperprolactinemia are among the endocrinologic disorders implicated in approximately 17% to 20% of RPL. The prevalence of hypothyroidism in the general population of reproductive age is about 2-3%. The aim of this study is to observe the benefit of screening for hypothyroidism amongst women with recurrent spontaneous abortion early in the first trimester. The study included one hundred and sixty (160) women, in the reproductive age of life, where there ages ranged from 20 – 33 years, and divided into two groups. Study group which included eighty (80), non pregnant women with a history of two or more consecutive spontaneous abortions early in the first trimester, with no living children and control group which included eighty (80), non pregnant women having one or more living children without any history of abortion. Hypothyroidism was noted in ten (10) cases (12.5%) in the study group and noted in two (2) cases (2.5%) in the control group with a statistically significant difference (P < 0.01). The mean levels of TSH in the study group was 22.71  13.13 Iu/ml. Conclusion: Screening for hypothyroidism has clinical significance and would help to reduce miscarriage rate in women with recurrent spontaneous abortion.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Hui-fang Li ◽  
Qi-hong Shen ◽  
Xiao-qing Li ◽  
Zhang-feng Feng ◽  
Wei-min Chen ◽  
...  

Background. Shoutai Pill (STP), a famous classic herbal formula documented in traditional Chinese medicine (TCM), is widely available in China for treating unexplained recurrent spontaneous abortion (URSA). This systematic review and meta-analysis aims at evaluating the efficacy and safety of STP in the first trimester of pregnancy in women with a history of unexplained recurrent spontaneous abortion. Methods. The following eight databases were searched from their establishment to Dec 31, 2019, for randomized controlled trials (RCTs): PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese BioMedical database (CBM), Chinese Scientific Journal Database (VIP), and the Wanfang database. The quality of evidence was estimated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results. A total of 12 studies (916 patients) with URSA were contained in this meta-analysis. The forest plot showed that patients treated with Shoutai Pill and western medicine had a significantly lower incidence of early pregnancy loss (RR: 0.42; 95% CI: 0.34–0.52; P<0.01, I2=0%). Subgroup analysis revealed that different types of TCM syndrome differentiation had the similar results. Also, in the combined group, patients had a lower TCM syndromes and symptoms and serum D-dimer level, while higher incidence of live birth. Conclusions. Our findings suggest that cotreatment with STP and western medicine might be superior to western medicine alone in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent spontaneous abortion, and there was no adverse event in the experimental group reported. However, the methodological quality of included RCTs was unsatisfactory; it is necessary to verify its effectiveness with further more standardized researches of rigorous design.


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