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Published on: August 11, 2012
MicroRNA mediated regulation of oxidative stress and cytokines in Chlamydia trachomatis-infected recurrent
Ankita Ray1, Dibyabhaba Pradhan2, Fouzia Siraj3
1Molecular Microbiology laboratory, ICMR-National Institute of Pathology, Sriramachari Bhawan, Safdarjung hospital campus, New Delhi, India.
Problem:
Increased oxidative stress (OS) and inflammatory responses are major underlying factors behind Chlamydia trachomatis-associated recurrent spontaneous abortion (RSA). miRNAs are known to regulate inflammation and OS and their dysregulation has been associated with compromised pregnancies. Therefore, aim of this study was to investigate the expression/correlation of OS biomarkers, cytokines and miRNAs in C. trachomatis-associated RSA.
Method Of Study:
Urine and non-heparinized blood samples were collected from RSA patients with history of >3 consecutive abortions (cases) and non-pregnant women with history of >2 successful deliveries (controls) attending Department of Obstetrics and Gynaecology, Safdarjung hospital, New Delhi. C. trachomatis detection was done in urine by PCR. miRNA expression was studied by microarray analysis and validated by real time-PCR. Evaluation of cytokines and antioxidant genes expression were done by real-time PCR. Level of OS biomarkers 8-hydroxy guanosine (8-OHdG) and 8-isporostane (8-IP) were measured by ELISA.
Results:
Fifty circulating miRNAs were differentially expressed in infected patients compared with controls. Of these, four were overexpressed and 46 downregulated. Thirteen differentially expressed circulating miRNAs were selected to validate microarray results. miRs-8069, -3663-3p showed maximum upregulation/downregulation in infected versus control group. Expression of cytokines (IL-8, TNF-α, IFN-γ), antioxidant genes SOD2 and OS biomarkers (8-OHdG,8-IP) were increased while SOD1 was decreased in infected patients. miR-8069 showed significant positive correlation with cytokines, SOD2, 8-OHdG and 8-IP. miR-3663-3p showed significant positive correlation with SOD1.
Conclusions:
Overall results indicate circulating miRNAs are involved in pathogenesis of C. trachomatis-associated RSA and are potential modulators of cytokine signalling and OS in infected RSA.
Insights
Circulating microRNAs (miRNAs) are implicated in Chlamydia trachomatis-associated recurrent spontaneous abortion (RSA). Dysregulated miRNAs correlate with oxidative stress and inflammation, suggesting their role in RSA pathogenesis.
Area of Science:
- Reproductive immunology
- Molecular biology
- Infectious diseases
Background:
- Increased oxidative stress (OS) and inflammation are key factors in Chlamydia trachomatis-associated recurrent spontaneous abortion (RSA).
- MicroRNAs (miRNAs) regulate inflammatory and OS pathways, and their dysregulation is linked to pregnancy complications.
Purpose of the Study:
- Investigate the expression and correlation of OS biomarkers, cytokines, and miRNAs in women with C. trachomatis-associated RSA.
- Identify potential miRNA biomarkers for C. trachomatis-associated RSA.
Main Methods:
- Collected urine and blood samples from RSA patients and healthy controls.
- Detected C. trachomatis using PCR.
- Analyzed miRNA expression via microarray and real-time PCR.
- Quantified cytokine and antioxidant gene expression using real-time PCR.
- Measured OS biomarkers (8-hydroxy guanosine and 8-isoprostane) via ELISA.
Main Results:
- Fifty circulating miRNAs were differentially expressed in RSA patients compared to controls.
- miR-8069 and miR-3663-3p showed significant upregulation/downregulation.
- Elevated levels of cytokines (IL-8, TNF-α, IFN-γ), SOD2, 8-OHdG, and 8-IP were observed in RSA patients.
- miR-8069 positively correlated with cytokines and OS biomarkers.
Conclusions:
- Circulating miRNAs play a role in the pathogenesis of C. trachomatis-associated RSA.
- These miRNAs may modulate cytokine signaling and OS in RSA.
- miRNAs represent potential diagnostic or therapeutic targets for RSA.
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