Increased nitric oxide production and gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats

Abstract

The lung is a fetal organ affected by maternal diabetes. Nuclear receptor PPARalpha is capable of regulating nitric oxide (NO) overproduction in different tissues. We aim to determine whether fetal lung PPARalpha protein expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARalpha regulation of NO production in the fetal lung. Diabetes was induced by streptozotocin administration to rat neonates. Fetal lung was explanted at term gestation and evaluated for PPARalpha expression and NO production. On day 19, 20 and 21, fetuses were injected with the PPARalpha ligand LTB4, and the fetal lung explanted on day 21 for evaluation of PPARalpha and the inducible isoform of nitric oxide synthase (iNOS). Besides, pregnant rats were fed with diets enriched in PPAR ligands (olive and safflower oils) for further evaluation of fetal lung NO production and PPARalpha expression on day 21. We found reduced PPARalpha concentrations only in the lung from male fetuses from the diabetic group when compared to controls, although maternal diabetes led to NO overproduction in both male and female fetal lungs. Fetal activation of PPARalpha lead to changes in lung PPARalpha expression only in female fetuses, although this treatment increased iNOS expression in both male and female fetuses in the diabetic group. Diets enriched in olive oil and not in safflower oil led to a reduction in NO production in both male and female fetal lungs. In conclusion, there are gender dependent changes in PPARalpha expression and signaling in the fetal lung from diabetic rats, although PPARalpha activation prevent maternal diabetes induced lung NO overproduction in both male and female fetuses.