Chlamydia trachomatis is considered to be an important infectious etiology behind RSA. Several studies have established an association between C. trachomatis infection and RSA (Baud et al., 2011, Visnovsky et al., 2013). Spontaneous aborters with chlamydial infection have higher risk of ascending infection and increasing probability of HIV and cervical cancer (Adachi et al., 2016). Prevalence of 15–17 % of C. trachomatis has been diagnosed in RSA patients in endometrial tissue (Singh et al., 2020) and urine (Ray et al., 2021) by PCR in Indian women. Serological studies in India have revealed a prevalence of 26 % in RSA patients versus pregnant women (Avasthi et al., 2003). However, there is paucity of literature on the mechanism of pathogenesis and immune-molecular pathways leading to RSA.

MicroRNAs (miRNA/miR) play critical role in reproductive disorders (Santamaria et al., 2014) and have important pathological implications in gynecological processes (Javadi et al., 2021). miRNAs present in biological fluids are resistant to ribonucleases and their aberrant expression in adverse pregnancy outcomes such as RSA has also been reported (Prieto and Markert, 2011). The aberrant expression of miRNAs affects the target genes involved in downstream signaling pathways. For instance, expression of miR-101-3p contributes to trophoblast cell apoptosis by targeting ERp44 leading to development of RSA (Zou et al., 2014). miR- 146b-5p targets and inhibits MMP gene which plays pivotal role in migration/invasion of trophoblast cells required for implantation, the dysregulation of which can lead to RSA (Li and Li, 2016). Pathogens are known to alter their host miRNA expression for their own survival (Eledge and Yeruva, 2018). In case of infection with C. trachomatis, expression of miRNAs leads to activation of inflammatory associated pathways regulating host immune response to infection (Derrick et al., 2013).

miRNAs are known to regulate the expression of reproductive hormones and immune molecules such as cytokines. Cytokines being essential immune system messengers also have a role in pregnancy success at different stages (such as effective embryo implantation and proliferation and differentiation of the trophoblast) as well as protection and pathogenesis during bacterial or viral infection (Yockey and Iwasaki, 2018). miRNAs contribute towards successful implantation process and its failure may have an immunologic basis and altered cytokine milieu in RSA women (Bidarimath et al., 2014). The role of endocrine hormones like progesterone has been well indicated in the etiology of recurrent abortions (Deng et al., 2022). It plays a critical role throughout the menstrual cycle regulating various reproductive processes such as ovulation, endometrium proliferation, egg maturation and pregnancy maintenance. A study reported expression of miRs-451, 424, 125 and 30b to be lower in women with high blood progesterone levels compared to those with low blood progesterone levels (Altmäe et al., 2012).

Progesterone is also a potent immunomodulatory as it modulates cytokine production pattern (Lissauer et al., 2015). Previously it has been reported that peripheral blood mononuclear cells from women with a history of RSA produced lower levels of the pro-inflammatory cytokines in the presence of progesterone (Abdul Hussain et al., 2020) suggesting its ability to redirect the cytokine population.

Studies on C. trachomatis-infection and miRNAs involved in immunoregulatory mechanisms leading to compromised pregnancy such as RSA is still in infancy and warrants further research. There is a definite need for understanding the pathophysiology behind maternal fetal rejection leading to RSA. The present study investigated selected serum miRNA expression viz.: miR-133a, -101-3p, -146b-5p, -320b, -24, -559 in women with history of RSA infected with C. trachomatis. Further, progesterone estimation and expression of few cytokines were studied and correlated with expression of miRNAs.