Abstract
ObjectiveWe 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.MethodCell morphology and collagen microstructure was investigated by scanning electron microscopy and second harmonic generation in fetal membranes taken from women who underwent fetal surgery. Immunofluoresence and real‐time quantitative polymerase chain reaction was used to examine Cx43 expression in control and wound edge AM.ResultsScanning electron microscopy 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 with controls (p < 0.001), with preferential distribution in the fibroblast layer compared with 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 with controls (p < 0.001).ConclusionOverexpression of Cx43 in the AM after fetal surgery induces morphological and structural changes in the collagenous matrix that may interfere with normal healing mechanisms. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
Highlights
Mechanical rupture of the fetal membranes can occur as a result of trauma and after invasive prenatal interventions such as open fetal surgery, fetoscopy or amniocentesis leading to iatrogenic preterm premature rupture of the fetal membrane (PPROM)
The present study examined whether surgically induced membrane defects after fetoscopic surgery increase connexin 43 (Cx43) expression in the wound edge of the amniotic membrane (AM) and drives structural changes in collagen architecture
Thinner and longer length fibres were observed in the chorionic membrane (CM), but the microstructure mainly consisted of a discrete network of collagen along the wound edge
Summary
Mechanical rupture of the fetal membranes can occur as a result of trauma and after invasive prenatal interventions such as open fetal surgery, fetoscopy or amniocentesis leading to iatrogenic preterm premature rupture of the fetal membrane (PPROM). The demand for fetal surgery is increasing as it has become evident that in some conditions, treatment in utero improves long-term outcome. Fetoscopic laser ablation is routinely performed for advanced twin-to-twin transfusion syndrome (TTTS), and fetal repair of congenital myelomeningocele has been shown to improve motor function postnatally.[1,2] spontaneous healing of the defect in the amniotic membrane (AM) does not occur after fetoscopic surgery, and a visible membrane defect is left, which is prone to rupture.[3,4,5] PPROM complicates over 30% of fetal surgeries that are being used to treat abnormalities in the unborn baby. PPROM and subsequent preterm birth compromises the outcome of treated babies, reducing the clinical effectiveness of fetal surgery. There are no clinical solutions to improve healing of the fetal membranes after they rupture.[6,7,8]
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