Tensile strain increased COX-2 expression and PGE2 release leading to weakening of the human amniotic membrane

Abstract Introduction There is evidence that premature rupture of the fetal membrane at term/preterm is a result of stretch and tissue weakening due to enhanced prostaglandin E 2 (PGE 2 ) production. However, the effect of tensile strain on inflammatory mediators and the stretch sensitive protein connexin-43 (Cx43) has not been examined. We determined whether the inflammatory environment influenced tissue composition and response of the tissue to tensile strain. Methods Human amniotic membranes isolated from the cervix ( C AM) or placenta regions ( P AM) were examined by second harmonic generation to identify collagen orientation and subjected to tensile testing to failure. In separate experiments, specimens were subjected to cyclic tensile strain (2%, 1 Hz) for 24 h. Specimens were examined for Cx43 by immunofluorescence confocal microscopy and expression of COX-2 and Cx43 by RT-qPCR. PGE 2 , collagen, elastin and glycosaminoglycan (GAG) levels were analysed by biochemical assay. Results Values for tensile strength were significantly higher in P AM than C AM with mechanical parameters dependent on collagen orientation. Gene expression for Cx43 and COX-2 was enhanced by tensile strain leading to increased PGE 2 release and GAG levels in P AM and C AM when compared to unstrained controls. In contrast, collagen and elastin content was reduced by tensile strain in P AM and C AM. Discussion Fibre orientation has a significant effect on amniotic strength. Tensile strain increased Cx43/COX-2 expression and PGE 2 release resulting in tissue softening mediated by enhanced GAG levels and a reduction in collagen/elastin content. Conclusion A combination of inflammatory and mechanical factors may disrupt amniotic membrane biomechanics and matrix composition.