Stretch-sensitive protein causes foetal membrane rupture

Premature rupture of the foetal membrane is the result of stretch-sensitive protein suggests research from two of London’s leading universities. A team from University College London and Queen Mary University of London believe that PPROM – pre-term premature rupture of the foetal membrane – could be caused by connexion 43 (Cx43). An overproduction of prostaglandin E2 (PGE2) caused by overstretching the amniotic membrane activates the protein and reduces the mechanical properties of the membrane. This failure could account for 40% of pre-term births, the main reason for infant death worldwide. “To have potentially found a way to reduce pre-term births and prevent early deaths of young babies worldwide is incredibly exciting,” said Dr Tina Chowdhury from QMUL. “The unique bioengineering tools at QMUL have allowed is to test the tissue in a way that has never been done before. This gives us an understanding of both the mechanical as well as biological mechanisms involved and will help us to develop therapies that will reduce the number of pre-term births.” Human amniotic membranes were isolated from the cervix or placenta regions and examined to identify collagen orientation, before being subjected to tensile testing failure. Separate experiments subjected the specimens to cyclic tensile strain for 24 hours; these samples were then examined for Cx43 by immunofluorescence confocal microscopy. Researchers found values for tensile strength were significantly higher in placental rather than cervical amniotic membranes with mechanical parameters dependent on the collagen orientation. Gene expression for Cx43 was enhanced by tensile strain, leading to increased PGE2 release in both sets of samples. Increased Cx43 expression and PGE2 release resulted in tissue softening and a reduction in collagen and elastin content, potentially causing an early rupture. “Our findings have provided a new understanding of why pregnant women who have pre-term contractions go on to rupture their membranes early,” said Dr Anna David, a consultant in obstetrics and pre-term birth from UCL’s Institute for Women’s Health. “This has the potential to save many lives worldwide and improve the health and well-being of women during pregnancy and their families after birth. The study, published in Placenta was funded by Wellbeing of Women and Rosetrees Trust. Tensile strain increased COX-2 expression and PGE2 release leading to weakening of the human amniotic membrane