Metabolic syndrome mediates inflammatory and oxidative stress responses in patients with recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. Exaggerated maternal immune response and oxidative stress status have been proposed as one of the main underlying mechanisms for RPL. The aim of this study was to evaluate the role of inflammatory pathway and oxidative stress imbalance in RPL patients with or without metabolic syndrome (MetS). 21 and 28 RPL patients with (RPL-MS) and without (RPL-NMS) metabolic syndrome were enrolled in this clinical study. 42 healthy women also were considered as the control group. The levels of IL1 beta, IL6, IL17, TNF alpha, CCL2, CXCL8 were evaluated by ELISA method. Additionally, the oxidative stress biomarkers including TAS, TOS, NO, CAT, SOD, AOPP, MPO were analyzed by spectrophotometry. The expression levels of IL1 beta, IL6, IL17, TNF alpha, CCL2, CXCL8, NF kappa B, AP1, miR-21, miR-146-a, miR-223 were also assessed by real time PCR. The frequency of Th17 and T-reg cells was also measured by flow cytometry. Significant increase in the expression levels of IL1 beta, IL6, IL17, TNF alpha, CCL2, CXCL8, NF kappa B, AP1 and miR-21 was observed in RPL-MS patients. Furthermore, significant decreased expression levels of FoxP3, miR-146-a and miR-223 was also observed in RPL-MS group. The levels of IL1 beta, IL6, IL17, TNF alpha, CCL2, CXCL8, NO, MPO and TOS were found to be higher in RPL-MS group compared to the RPL-NMS and healthy controls. In contrast, the level of CAT and SOD in RPL-MS patients was decreased. The frequency of Th17 and Treg cells was also higher and lower in RPL-MS patients compared to the other groups, respectively. Our results support the concept that subclinical inflammatory state, oxidative stress and metabolic syndrome play a crucial role in the etiopathogenesis of RPL assisting clinicians for pregnancy consequences prediction.