Investigation of IL-6 Expression in Placentas with Term and Preterm Premature Membrane Rupture

Aim: This study investigated IL-6 expression in placentas of patients diagnosed with preterm and term premature rupture of membranes (PROM) via immunohistochemical and in silico analysis. Materials and Methods: Placentas of 40 healthy patients and 40 preterm and 40 term patients diagnosed with term PROM who gave birth in Gynecology and Obstetrics Clinic of XXX University were subjected to histological tissue embedding protocol. IL-6 immunostaining was performed on tissues. Bioinformatic analysis was performed to explore the potential molecular mechanisms underlying role of IL-6 role in PROM. Results: IL-6 expression was generally negative in control group however significantly higher in both preterm PROM and term PROM groups, but no significant difference in between preterm and term PROM groups. In preterm PROM group, IL-6 was recorded as positive in areas with cytotrophoblast, syncytiotrophoblast and fibrinoid accumulation, but was negative in villus connective tissue cells and vascular endothelium. In EMR group, intense IL-6 expression was observed in trophoblastic layer, syncytial nodes and fibrinoid accumulation, but was generally negative in villous stromal and vascular endothelial cells. Enrichment analysis of IL-6-associated potential PROM targets revealed significant pathways related to microbial responses such as cellular response to lipopolysaccharide, molecule of bacterial origin and biotic stimuli, indicating that IL-6 may modulate PROM predominantly through these pathways. Conclusion: Compared to control group, significant histopathological changes and increased IL-6 expression were observed in preterm PROM and term PROM groups, with in-silico analysis, indicating PROM increased placental inflammation and damage via IL-6.