title: VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen.
abstract: Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.
authors: Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão PretoSP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors: L
authors: L
authors: Sbragia
authors: Departamento de Hidrobiologia do Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São CarlosSP, Brasil, Departamento de Hidrobiologia do Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil.
authors: A C C
authors: AC
authors: Nassr
authors: Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão PretoSP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors: F L L
authors: FL
authors: Gonçalves
authors: Pediatrics House Office, Cincinnati Children's Hospital Medical Center, CincinnatiOH, USA, Pediatrics House Office, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: A F
authors: AF
authors: Schmidt
authors: Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CampinasSP, Brasil, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors: C C
authors: CC
authors: Zuliani
authors: Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, CampinasSP, Brasil, Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brasil.
authors: P V
authors: PV
authors: Garcia
authors: Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão PretoSP, Brasil, Divisão de Cirurgia Pediátrica, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
authors: R M
authors: RM
authors: Gallindo
authors: Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, CampinasSP, Brasil, Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brasil.
authors: L A V
authors: LA
authors: Pereira
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D065630:Hernias, Diaphragmatic, Congenital / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000196:embryology; D010647:Phenyl Ethers; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*
chemical_list: D010647:Phenyl Ethers; D040262:Receptors, Vascular Endothelial Growth Factor; C007350:nitrofen