scholarly journals Decreased Toll-like Receptor (TLR) 2 and 4 Expression in Spermatozoa in Couples with Unexplained Recurrent Spontaneous Abortion (URSA)

2020 ◽  
Author(s):  
Nasrin Sereshki ◽  
Alireza Andalib ◽  
Ataollah Ghahiri ◽  
Ferdos Mehrabian ◽  
Roya Sherkat ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Toll Like Receptor 2 ◽  
And Control ◽  
Reproductive Processes

Studies have shown that toll-like receptors (TLRs) play some important roles in reproductive processes such as ovulation, spermatogenesis, sperm capacitation, fertilization, and pregnancy to the best of our knowledge, no study has evaluated the expression and role of these molecules and their impairment in spermatozoa; accompanied by pregnancy complications such as recurrent spontaneous abortion (RSA). Therefore, this study investigates the alteration of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) expression in spermatozoa in men whose spouse have unexplained RSA. Fifteen fertile couples and fifteen couples with unexplained recurrent spontaneous abortion (URSA) were included in this study. The level of TLR2 and TLR4 expression in untreated and lipopolysaccharide (LPS) or PAM3CYS in treated spermatozoa were examined by flow cytometry. The results showed reduced expression of TLR4 in untreated spermatozoa and decreased LPS or PAM3CYS levels in treated spermatozoa in the URSA group compared to the control group. No significant differences were found in TLR2 expression of untreated spermatozoa in RSA and control groups. After the treatment of spermatozoa with LPS, the TLR2 expression was decreased in both groups. After the treatment of spermatozoa with PAM3CYS, the level of TLR2 expression was significantly increased in the URSA group; while no significant differences were shown in the control group in comparison to untreated spermatozoa. We have concluded that decreased TLR4 expression and a differently increased TLR2 expression in response to ligand treatment in spermatozoa is associated with URSA.

Expression of C-type lectin receptors and Toll-like receptors in decidua of patients with unexplained recurrent spontaneous abortion

2017 ◽  
Vol 29 (8) ◽  
pp. 1613 ◽  
Author(s):  
Liang Xu ◽  
Tian Qiu ◽  
Yudong Wang ◽  
Yan Chen ◽  
Weiwei Cheng
Keyword(s):  
Mrna Expression ◽  
Spontaneous Abortion ◽  
Transforming Growth Factor ◽  
Recurrent Spontaneous Abortion ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Toll Like Receptors ◽  
Lectin Receptors ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Normal Controls

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.

scholarly journals Evaluation of the Effects of 1,25VitD3 on Inflammatory Responses and IL-25 Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Nana Li ◽  
Nafiseh Saghafi ◽  
Zahra Ghaneifar ◽  
Seyed Abdorahim Rezaee ◽  
Houshang Rafatpanah ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Blood Mononuclear Cells

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.

scholarly journals Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1205
Author(s):  
Małgorzata Sobstyl ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Rafał Hrynkiewicz ◽  
Dominika Bębnowska ◽  
Izabela Korona-Głowniak ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Screening Tests ◽  
Control Group ◽  
Newly Diagnosed ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Diagnostic Approaches ◽  
Toll Like Receptor 2 ◽  
Marker Molecule

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.

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

2021 ◽  
Author(s):  
Shiyu Bai ◽  
Shuai Fu ◽  
Liqiong Zhu ◽  
Manqi Chen ◽  
Bingqian Huang ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Early Pregnancy ◽  
Uterine Cavity ◽  
First Trimester ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Microbial Composition ◽  
Double Lumen ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Rrna Sequencing

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.

scholarly journals Key Gene and Functional Pathways Identified in Unexplained Recurrent Spontaneous Abortion Using Targeted RNA Sequencing and Clinical Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Heng Gu ◽  
Longyu Li ◽  
Mengxuan Du ◽  
Hang Xu ◽  
Mengge Gao ◽  
...  
Keyword(s):  
Differential Expression ◽  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Hub Genes ◽  
Significant Differential Expression ◽  
Qrt Pcr ◽  
Significant Difference ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Ifn Γ

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.

Immunopharmacological properties of VitD3: 1,25VitD3 modulates regulatory T cells and Th17 cells and the cytokine balance in PBMCs from women with unexplained recurrent spontaneous abortion [URSA]

2021 ◽  
Vol 14 ◽  
Author(s):  
Jiefan Gao ◽  
Li Wang ◽  
Lei Bu ◽  
Yangyang Song ◽  
Xiao Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Spontaneous Abortion ◽  
Th17 Cells ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Case Group ◽  
Gene Expressions ◽  
Unexplained Recurrent Spontaneous Abortion

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.

scholarly journals WNT7A (rs104893832) polymorphism increases the risk of recurrent spontaneous abortion in Iranian women

2018 ◽  
Vol 37 (3) ◽  
pp. 167
Author(s):  
Manouchehr Mazdapour ◽  
Mahmood Dehghani Ashkezari ◽  
Seyed Morteza Seifati
Keyword(s):  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Chi Square ◽  
Pcr Rflp ◽  
History Of ◽  
Spss Software ◽  
And Control ◽  
Regression Tests ◽  
Control Study

BACKGROUND<br />Recurrent spontaneous abortion is defined as the occurrence of three or more clinical miscarriages in one woman. Several factors, including genetics and environmental factors, are involved in this kind of infertility, in which WNT7A (rs104893832) polymorphism plays a major role. The aim of the present study was to determine the association between a common polymorphism of WNT7A (rs104893832) with recurrent spontaneous abortion in females. <br /><br />METHODS<br />In the present case-control study, the WNT7A (rs104893832) polymorphism was investigated in 70 women with recurrent spontaneous abortion as cases and 100 women with at least one child and no history of infertility or abortion as controls. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was used to investigate the WNT7A (rs104893832) polymorphism in both case and control groups. The data were subsequently analyzed using the chi-square and logistic regression tests by SPSS software (version 18.0). <br /><br />RESULTS<br />A significant association was found between the WNT7A (rs104893832) polymorphism and recurrent spontaneous abortion (OR=25.00, 95% CI=5.52-157.09; p&lt;0.0001). Our finding showed that G allele frequency in women with recurrent spontaneous abortion was significantly different compared to the control group. (OR=6.42, 95% CI=2.82-15.16; p&lt;0.0001).Therefore, genetic variation in WNT7A (rs104893832) polymorphism may play a role in recurrent spontaneous abortion. <br /><br />Conclusion<br />This study revealed that WNT7A (rs104893832) polymorphism increased the risk of recurrent spontaneous abortion. Knowledge of these mutations and polymorphisms can provide an insight into the prognosis for individual patients. Therefore, further studies are necessary to establish the association of WNT7A (rs104893832) polymorphism with recurrent spontaneous abortion in a larger population.

scholarly journals Peptidoglycan of Staphylococcus aureus Upregulates Monocyte Expression of CD14, Toll-Like Receptor 2 (TLR2), and TLR4 in Human Blood: Possible Implications for Priming of Lipopolysaccharide Signaling

2005 ◽  
Vol 73 (11) ◽  
pp. 7613-7619 ◽  
Author(s):  
J. S. Hadley ◽  
J. E. Wang ◽  
S. J. Foster ◽  
C. Thiemermann ◽  
C. J. Hinds
Keyword(s):  
Human Blood ◽  
Priming Effect ◽  
Ex Vivo ◽  
Experimental Period ◽  
Cytokine Release ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Twofold Increase ◽  
Toll Like Receptor 2

ABSTRACT Previous studies have indicated that peptidoglycan (PepG) from gram-positive bacteria can exert a priming effect on the innate immune response to lipopolysaccharide (LPS) from gram-negative bacteria. Here, we hypothesized that this priming effect may be preceded by enhanced expression of monocyte CD14, Toll-like receptor 2 (TLR2), and TLR4. In an ex vivo whole human blood model, we observed a substantial synergy between LPS and PepG in the release of tumor necrosis factor alpha and interleukin-1β (IL-1β) over the 24-h experimental period, whereas the effect on IL-8 and IL-10 release was more time dependent. The priming effect of PepG on cytokine release was preceded by a rapid upregulation of CD14, TLR2, and TLR4 expression on monocytes: at 3 hours there was a twofold increase in CD14 expression (P < 0.03), a fivefold increase in TLR2 expression (P < 0.03), and a twofold increase in TLR4 expression (P < 0.03). CD14 and TLR2 remained upregulated throughout the experimental period following exposure to PepG (P < 0.05). Only a transient upregulation of these monocyte receptors was observed following treatment with LPS or LPS plus PepG. In conclusion, the synergistic effect of LPS and PepG on cytokine release is preceded by a reciprocal upregulation of TLR2 and TLR4 by both bacterial cell wall components.

scholarly journals Effect of Vitamin D Supplementation on Unexplained Recurrent Spontaneous Abortion: A Double-Blind Randomized Controlled Trial

2016 ◽  
Vol 9 (3) ◽  
pp. 95 ◽  
Author(s):  
Mansoureh Samimi ◽  
Fatemeh Foroozanfard ◽  
Farzaneh Amini ◽  
Mojtaba Sehat
Keyword(s):  
Vitamin D ◽  
Spontaneous Abortion ◽  
Vitamin D3 ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Recurrent Spontaneous Abortion ◽  
Control Groups ◽  
Double Blind ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
And Control

<p><strong>BACKGROUND:</strong> Recurrent spontaneous abortion is a serious problem in pregnancy, which affects between 2 and 5% of women of reproductive age. This study was designed to examine the effect of vitamin D supplementation on the occurrence of unexplained recurrent spontaneous abortion (URSA).</p><p><strong>METHODS:</strong> A double-blind randomized and controlled clinical trial was performed on 80 patients with URSA. They were treated with vaginal progesterone (400 IU/day) after confirmation of pregnancy and received vitamin D and placebo in two intervention (n=40) and control groups (n=40), respectively. The incidence of abortion and the serum levels of IL-23 were examined within 20 weeks of gestation.</p><p><strong>RESULTS:</strong> The levels of vitamin D3 prior to the start of the study were equal to 11.65±3.76 ng/ml and 11.53±2.39 ng/ml (p=0.86) in the intervention and control groups, respectively, which were decreased to 13.21±3.47 ng/ml and 11.08±2.76 ng/ml (p=0.004) at the end of the study, when the mean serum levels of IL-23 were equal to 18.4±3.78 pg/ml and 23.16±4.74 pg/ml in the two groups (p &lt;0.004). The frequency of abortion in the control and intervention groups was equal to 5 (12.8%) and 13 (34.2%), respectively (p=0.03, OR=3.53, 95% CI= 1.12-11.2).</p><p><strong>CONCLUSIONS:</strong> Vitamin D3 leads to decreased serum levels of IL-23 and incidence of abortion among women with URSA.</p>

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