Connexin 43 is overexpressed in human fetal membrane defects after fetoscopic surgery

OBJECTIVE: We examined whether surgically induced membrane defects elevate connexin 43 (Cx43) expression in the wound edge of the amniotic membrane (AM) and drives structural changes in collagen that affects healing after fetoscopic surgery. METHOD: Cell morphology and collagen microstructure was investigated by SEM and SHG in fetal membranes taken from women who underwent fetal surgery. IMF and RT-qPCR was used to examine Cx43 expression in control and wound edge AM. RESULTS: SEM showed dense, helical patterns of collagen fibrils in the wound edge of the fetal membrane. This arrangement changed in the fibroblast layer with evidence of collagen fibrils that were highly polarised along the wound edge but not in control membranes. Cx43 was increased by 112.9% in wound edge AM compared to controls (p < 0.001), with preferential distribution in the fibroblast layer compared to the epithelial layer (p < 0.01). In wound edge AM, mesenchymal cells had a flattened morphology and there was evidence of poor epithelial migration across the defect. Cx43 and COX-2 expression was significantly increased in wound edge AM compared to controls (p < 0.001). CONCLUSION: Overexpression of Cx43 in the AM after fetal surgery induces morphological and structural changes in the collagenous matrix that may interfere with normal healing mechanisms