Influence on Bladder Development of Prenatal Treatment of Surgically Induced Myelomeningocele in a Sheep Model

Abstract

Purpose To assess if a surgically induced model of myelomeningocele (MMC) in sheep produces bladder malformations like those observed in human disease and to determine if fetal surgical repair allows normal bladder development. Material and Methods A MMC was created in 20 fetal lambs between 60 and 80 days of gestation. Ten of them did not undergo fetal repair (group A), 5 were repaired with an open two-layer closure (group B) and 5 with fetoscopic coverage using bioglue (group C). Clinical assessment of motor and urinary behaviour was performed at term. Bladders were examined externally and in transversal sections. Histological changes were assessed using H-E and Masson stained sections. Three normal lambs served as control. Results Five lambs in group A (50%), 2 in group B (40%) and 3 in group C (60%) were delivered at term (day 140) and sacrificed within 24 hours. Lambs in group A were paraplegic and incontinent for urine. Macroscopically, bladders were severely dilated and thin. Microscopically they showed some fibrous tissue lying immediately subjacent to the epithelium that was obviously thinner than controls. Muscular layer was thin and partially disrupted. Lambs in group C showed normal histological structure with mild epithelium changes and moderate thinning of the muscular layer. Bladders in group B and in control animals showed none of these changes. Conclusions Some of the bladder abnormalities associated to MMC in human patients are also found in the uncorrected fetal lamb model. Open two-layer prenatal closure could prevent completely these malformations