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

KURTZ M; MARTÍNEZ N; CAPOBIANCO E; HIGA R; FORNES D; JAWERBAUM A

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2012 vol. 15 p. 120 - 127

0303-7207

The fetal lung is affected by maternal diabetes. Nuclear receptor PPARa regulates nitric oxide (NO) overproduction in different tissues. We aimed to determine whether fetal lung PPARa expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARa regulation of NO production in the fetal lung. Fetal lungs from control and diabetic rats were explanted on day 21 of gestation and evaluated for PPARa expression and NO production. Fetuses were injected with the PPARa ligand LTB4 on days 19, 20 and 21, and the fetal lung explanted on day 21 to evaluate PPARa and the inducible isoform of NO synthase (iNOS). Besides, pregnant rats were fed with olive oil- and safflower oil-supplemented diets, enriched in PPAR ligands, for evaluation of fetal lung NO production and PPARa expression. We found reduced PPARa 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 PPARa led to changes in lung PPARa expression only in female fetuses, although this treatment increased iNOS expression in both male and female fetuses in the diabetic group. Diets supplemented with olive oil and not with safflower oil led to a reduction in NO production in male and female fetal lungs. In conclusion, there are gender-dependent changes in PPARa expression and signaling in the fetal lung from diabetic rats, although PPARa activation prevents maternal diabetes-induced lung NO overproduction in both male and female fetuses.