Abstract

Objective To investigate ultrastructure and molecular change of kidneys after correction of partial unilateral ureteral obstruction. Methods The 26 fetal lambs at 75-85 days of gestation were divided into 3 groups. Obstructed group: partial unilateral ureteral obstruction was achieved with intrauterine surgery in 12 fetal lambs. Decompressed group: partial unilateral ureteral obstruction in 10 fetal lambs first was released 3 weeks later by intrauterine surgery. Control group: a sham operation was performed. The kidneys of the lambs were removed after birth to study the transformation of podocytes as well as expression of paired-box 2 (PAX2) and vascular endothelial growth factor (VEGF). Results Overall, 21 fetal lambs survived: 9 from the obstructed group, 8 from the decompressed group, and 4 from the control group. Compared with the control kidneys, the obstructed kidneys showed cysts of various sizes in the cortex, fibrosis of the interstitial tissue, significantly decreased number of glomeruli, severer podocyte foot process fusion (4. 20 ± 1. 08% vs 86.79 ± 1. 66%) , markedly increased PAX2 (1. 43 ± 0. 09 vs 2. 44 ± 0. 09) and decreased VEGF expressions (0. 80 ± 0. 15 vs 0. 33 ± 0. 14). However, in the decompressed kidneys, the cystic changes decreased, number of glomeruli increased, but extracellular matrix (ECM) deposition was still obvious, fusion of the podocyte foot processes was reduced (41. 18±3. 13% vs 86. 79± 1. 66%), VEGF expression was significantly increased (2. 08 ± 0. 21 vs 0. 33 ± 0. 14) , and expression of PAX2 was restored to some extent (2. 05 ± 0. 14 vs 2. 44 ± 0. 09) in decompressed kidneys. Conclusions Relief of obstruction in utero can reverse the development of nephropathy, evidenced by the phenotype transformation of podocytes, expression of PAX2 and VEGF. Key words: Hydronephrosis,congenital; Ureteral obstruction; Podocytes; Vascular endothelial growth factor

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