Increased nitric oxide production and gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats.
The fetal lung is affected by maternal diabetes. Nuclear receptor PPARα regulates nitric oxide (NO) overproduction in different tissues. We aimed to determine whether fetal lung PPARα expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARα 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 PPARα expression and NO production. Fetuses were injected with the PPARα ligand LTB(4) on days 19, 20 and 21, and the fetal lung explanted on day 21 to evaluate PPARα 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 PPARα expression. We found reduced PPARα 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 PPARα led to changes in lung PPARα 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 PPARα expression and signaling in the fetal lung from diabetic rats, although PPARα activation prevents maternal diabetes-induced lung NO overproduction in both male and female fetuses.
Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155 (1121ABG) Buenos Aires, Argentina.
Melisa
M
Kurtz
Nora
N
Martínez
Evangelina
E
Capobianco
Romina
R
Higa
Daiana
D
Fornes
Verónica
V
White
Alicia
A
Jawerbaum
D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004032:Diet; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020567:Fetal Weight; D005333:Fetus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D007975:Leukotriene B4 / Q000008:administration & dosage; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D009569:Nitric Oxide / Q000378:metabolism*; D000069463:Olive Oil; D009929:Organ Size; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D010938:Plant Oils / Q000008:administration & dosage; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017208:Rats, Wistar; D012450:Safflower Oil / Q000008:administration & dosage; D012737:Sex Factors; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D000069463:Olive Oil; D047493:PPAR alpha; D010938:Plant Oils; D014280:Triglycerides; D007975:Leukotriene B4; D009569:Nitric Oxide; D012450:Safflower Oil