Progesterone-mediated immunoregulation of cytokine signaling by miRNA-133a and 101-3p in Chlamydia trachomatis-associated recurrent spontaneous abortion

Abstract

miRNAs regulate the expression of various genes involved in cellular and metabolic pathways in pregnancy related complications including recurrent spontaneous abortion (RSA). Modulation of progesterone and associated pro-inflammatory cytokines by miRNAs in Chlamydia trachomatis-associated RSA is still under investigation. Present study aimed to evaluate the expression/correlation of serum-circulating miRNAs-133a, 101-3p, 320b, 146b-5p, 24, 559, progesterone and few cytokines in C. trachomatis-positive spontaneous aborters. Non-heparinized blood and urine was collected from 120 patients with history of RSA (Group I) and 120 patients with ≥ 2 successful deliveries (Group II) attending Department of Obstetrics and Gynecology, Safdarjung hospital, New Delhi, India. C. trachomatis detection was performed by PCR and chlamydial load by real time PCR. Progesterone concentration was estimated by ELISA. miRNAs and cytokine expression was studied by quantitative real-time PCR and correlated with progesterone expression. Twenty six patients were found to be positive for C. trachomatis. miRNAs- 133a, 101-3p showed maximum upregulation in infected versus control patients. miRNA expression showed positive correlation with chlamydial load. Progesterone concentration showed significant decrease while cytokines (IL-6, IFN-γ, TNF-α) were significantly upregulated in C. trachomatis-positive patients. Positive correlation was observed between expression of miRNAs-133a and 101-3p and cytokines while negative correlation was observed with progesterone in infected RSA patients. Correlation between progesterone and cytokines was found to be significantly negative in infected RSA patients. Although further validation is required, the study concludes that miR-133a and 101-3p are of clinical importance and have a role in immunoregulation of progesterone and cytokines in infection associated RSA.