CALL FOR PAPERS Programming Normal Renal Development and Modeling Disease Pathogenesis Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep

Galinsky R, Moss TJ, Gubhaju L, Hooper SB, Black MJ, Polglase GR. Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep. Am J Physiol Renal Physiol 301: F280–F285, 2011. First published May 18, 2011; doi:10.1152/ajprenal.00066.2011.— Chorioamnionitis is an antecedent of preterm birth. We aimed to determine the effect of experimental chorioamnionitis in fetal sheep during late gestation on 1) nephron number, 2) renal corpuscle volume, and 3) renal inflammation. We hypothesized that exposure to chorioamnionitis would lead to inflammation in fetal kidneys and adversely impact on the development of nephrons, leading to a reduction in nephron number. At 121 days of gestation (term 147 days), pregnant ewes bearing twin or singleton fetuses received a single intra-amniotic injection of lipopolysaccharide (n 6; 3 singletons, 3 twins); controls were either untreated or received an intraamniotic injection of saline (n 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At 128 days of gestation, fetuses were delivered via Caesarean section. Kidneys were collected and stereologically analyzed to determine nephron number and renal corpuscle volume. Renal inflammation was assessed using immunohistochemistry. Experimental chorioamnionitis did not affect body weight or relative kidney weight. There was a significant reduction in nephron number but no change in renal corpuscle volume in LPSexposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18% in singleton and twin LPSexposed fetuses, respectively. The degree of renal inflammation did not differ between groups. Importantly, this study demonstrates that exposure to experimental chorioamnionitis adversely impacts on nephron number in the developing fetus.