Pregnant rats were exposed to either
olive oil or 100 mg of
nitrofen on day 9.5 of gestation. Fetuses were recovered at term and divided into 3 groups: 1, control (n = 69); 2,
nitrofen without CDH (n = 25); and 3,
nitrofen with CDH (n = 40). Kidneys were dissected, weighed, and processed for biochemical measurements of
DNA,
proteins, total
retinol content, and for immunohistochemical staining of proliferating cells.
RESULTS: Kidneys were smaller in
nitrofen-exposed animals vs control animals (group 3, 0.65 +/- 0.08; group 2, 0.62 +/- 0.09 vs group 1, 0.73 +/- 0.09% of
body weight, P < .001), and there were no differences between right and left kidney weight in all the 3 groups. Regression of total kidney weight on
body weight showed a linear direct correlation between them in all the groups. Total amount of
DNA was significantly reduced in
nitrofen-exposed animals vs controls (group 3, 80.58 +/- 35.65; group 2, 64.71 +/- 20.28 vs group 1, 110.34 +/- 42.15 microg, P < .01), but the
DNA concentration remained the same in the 3 groups (group 3, 3.59 +/- 1.26; group 2, 3.06 +/- 1.19; group 1, 3.43 +/- 1.05 microg
DNA/mg kidney). Total
protein content (group 3, 1145.59 +/- 500.36; group 2, 993.2 +/- 276.62; group 1, 1287.48 +/- 312.52 microg),
protein concentration (group 3, 49.76 +/- 11.12; group 2, 43.95 +/- 6.79; group 1, 47.38 +/- 6.93 microg
protein/mg kidney), and
protein-to-
DNA ratio (group 3, 15.12 +/- 5.98; group 2, 16.22 +/- 6.85; group I, 16.16 +/- 7.02 microg/microg) were similar in all groups.
Retinol concentration was significantly reduced in both
nitrofen-exposed groups compared with the control group (group 3, 1.35 +/- 0.24; group 2, 1.28 +/- 0.11; group 1, 2.53+/-0.61 microg
retinol/g kidney). Proliferation index was similar in all 3 groups (group 3, 50.43 +/- 8.81; group 2, 47.96 +/- 6.01; group 1, 47.64 +/- 5.76% of proliferating cells).
CONCLUSIONS: Our data clearly show that renal enlargement in association with pulmonary hypoplasia is not seen in the
nitrofen-induced CDH. These results rule out any possible relationship between lung and kidney development. Moreover, kidneys are hypoplastic in both
nitrofen-exposed groups and have reduced
retinol content, suggesting that a
retinoid pathway disruption could be the common mechanism in the pathogenesis of lung and kidney hypoplasia in the
nitrofen model of CDH.