Inflammation-related downregulation of zonula Occludens-1 in fetal membrane contributes to development of prelabor rupture of membranes

Introduction: The aim of this research was to study the alteration of three key tight junction proteins, to explore whether they were involved in the occurrence of prelabor rupture of the membrane (PROM) and to determine the correlation with intrauterine infection. Methods: A total of 208 women were enrolled between January 2015 to December 2018, including those with preterm and term PROM (PROM group) and normal pregnancies with intact fetal membrane (control group). We investigated the expressions of three key TJ molecules (Zonula occludens-1, Occludin and Claudin-5) in fetal membranes. The localization and expression of Zonula occludens-1 (ZO-1) in the amnion and chorion were studied by immunohistochemistry assay. The associations between ZO-1 expression levels and extent of inflammatory reactions as well as other obstetric characteristics were further studied using Spearman's rank correlation test and Mann-Whitney U test. Results: ZO-1 was significantly downregulated in PROM group compared with control group (P < 0.001), whereas no significant changes were found for Occludin and Claudin-5. ZO-1 expression was reduced in the chorion and amnion layers in PROM group compared with that in control group, which showed a significant difference (P < 0.01), but no significant differences were observed between the preterm PROM and term PROM groups (P > 0.05). The expression levels of ZO-1 in the chorion were negatively correlated with the stage/grade of acute chorioamnionitis (P < 0.05). Discussion: Our study suggests that inflammation-related downregulation of ZO-1 might be a pivotal event in the occurrence of PROM, which helps to clarify the mechanism of membrane rupture caused by infection.