The effects of postnatal retinoic acid administration on nephron endowment in the preterm baboon kidney

Abstract

Administration of retinoic acid (RA), the active metabolite of vitamin A, is linked to the stimulation of nephrogenesis. The aim of this study was to determine whether early postnatal administration of RA could enhance ongoing nephrogenesis in a baboon model of premature birth. Unbiased stereological methods were used to estimate kidney volume, renal corpuscle volume, and nephron number. The percentage of abnormal glomeruli and the number of glomerular generations was also determined in the kidneys of preterm control (n = 6) and preterm +RA (n = 6) animals that received 500 microg/kg/d of all-trans RA after premature delivery. There was no significant difference between the preterm control and the preterm +RA groups in kidney size, nephron number (preterm control: 329,924 +/- 41,752; preterm +RA: 354,041 +/- 52,095; p = 0.59), renal corpuscle volume, number of glomerular generations, or the percentage of abnormal glomeruli. The proportion of abnormal glomeruli did not appear to be linked to any elements of postnatal care examined. The results of this study indicate that early postnatal administration of RA is unable to stimulate nephrogenesis in the kidney of the preterm baboon. Encouragingly, it does not appear to have any adverse effects on kidney development.

Figure 1

Photomicrograph of a neonatal baboon kidney indicating the glomerular generation counting method. Mature glomeruli were counted in a straight line along one side of a clearly distinguishable medullary ray (indicated by the black box) from the corticomedullary junction to the outer renal cortex. Scale bar = 100 μm.

Figure 2

Bar graph depicting the average nephron number (± SEM) of preterm control (n=6) and preterm +RA (n=6) animals.

Figure 3

Linear regression analyses of nephron number versus kidney volume in A preterm control (R² = 0.665, p = 0.047), and B preterm +RA (R² = 0.785, p = 0.019) animals.

Figure 4

Representative photomicrographs of WT-1 immunostaining of podocytes in normal and abnormal glomeruli from both preterm control (A normal; C abnormal) and preterm +RA animals (B normal; D abnormal). Scale bar = 50 μm.

Figure 5

Representative photomicrographs of in-situ hybridization of VEGF expression (dark purple stained nuclei) in podocytes of normal and abnormal glomeruli from preterm control (A normal; C abnormal) and preterm +RA animals (B normal; D abnormal). Scale bar = 50 μm.

Figure 6

Representative photomicrographs of CD31 immunostaining of endothelial cells in normal and abnormal glomeruli from preterm control (A normal; C abnormal) and preterm +RA animals (B normal; D abnormal). Scale bar = 50 μm.