title: Kidney development in the nitrofen-induced pulmonary hypoplasia and congenital diaphragmatic hernia in rats.
abstract: OBJECTIVE
  The relationship of the developing lung and kidney is not completely understood. Renal enlargement has been reported in association with pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Recent studies suggest that retinoids may be involved in the pathogenesis of CDH. The aims of this study were to investigate the effects of pulmonary hypoplasia on renal development and to evaluate retinoids status of kidneys in the nitrofen model of CDH.
  
  
  METHODS
  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.
authors.affiliation: The Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin 12, Ireland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Montedonico
authors.forename: Nana
authors.initials: N
authors.lastname: Nakazawa
authors.forename: Toko
authors.initials: T
authors.lastname: Shinkai
authors.forename: John
authors.initials: J
authors.lastname: Bannigan
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced* / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D007668:Kidney / Q000196:embryology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008168:Lung / Q000002:abnormalities* / Q000196:embryology; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D009929:Organ Size; D010647:Phenyl Ethers / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000502:physiology*; D014118:Toxins, Biological / Q000009:adverse effects
chemical_list: D010647:Phenyl Ethers; D012176:Retinoids; D014118:Toxins, Biological; C007350:nitrofen