Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep

TY - JOUR

T1 - Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep

AU - Galinsky, Robert

AU - Moss, Timothy

AU - Gubhaju, Lina

AU - Hooper, Stuart

AU - Black, Mary

AU - Polglase, Graeme

PY - 2011

Y1 - 2011

N2 - 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 approximately 121 days of gestation (term approximately 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 intra-amniotic injection of saline (n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At approximately 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 LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18 in singleton and twin LPS-exposed 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.

AB - 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 approximately 121 days of gestation (term approximately 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 intra-amniotic injection of saline (n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At approximately 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 LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18 in singleton and twin LPS-exposed 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.

UR - http://ajprenal.physiology.org/content/301/2/F280.full.pdf+html

U2 - 10.1152/ajprenal.00066.2011

DO - 10.1152/ajprenal.00066.2011

M3 - Article

VL - 301

SP - F280 - F285

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1522-1466

IS - 2

ER -