In utero tracheal occlusion: surgical approach associated to steroid treatment increase VEGF (Vascular Endothelial Growth Factor) receptors in lungs of fetal rats

Abstract

Background/Purpose: Congenital diaphragmatic hernia (CDH) presents with hypoplastic lungs and usually leads to pulmonary hypertension and high neonatal mortality. Fetal tracheal occlusion (TO) and prenatal corticotherapy are alternatives to accelerate fetal pulmonary growth and decrease hypoplasia in CDH. VEGF (Vascular Endothelial Growth Factor) production and surfactant production by type II pneumocytes are related with pulmonary maturityand are altered in CDH, but little has been described about VEGF receptors. Our objective was to quantify the receptors of VEGF (VEGFR) and type II pneumocytes, verifying the effects of TO and corticotherapy on normal lungs of fetal rats. Methods: Six groups of 12 Spreague-Dawley rat fetuses (gestation=22 days) were compared:TO, S (sham), C (control), TO+Dex, S+Dex and C+Dex. On the 18.5 gestational day, TO was performed with and without corticotherapy, using dexamethasone. On the 21.5 gestational daybody and lung weights were measured. Immunohistochemistry was carried out for VEGFR-1(Flt-1) and VEGFR-2 (Flk-1), as well as anti-SP-A, microscopic analysis and quantification of immune system marking. Results: Body weight decreased in Sham and lung weight increased in TO and TO+Dex (p<0.05) groups. VEGFR-1 and VEGFR-2 increased in TO and in TO+Dex (p<0.05). Type II pneumocytes (SP-A) decreased both in the TO and in TO+Dex groups in comparison with the Control groupin absolute value (p<0.05), with no differences in relative value to total cell count. Conclusion: TO in association with the use of corticosteroids increased VEGFR-1 and VEGFR-2, while the quantity of type II pneumocytes (SP-A) decreased in relation to the area considered, but not in relation to the total of pulmonary cells.