Conferencia: Placental programming in maternal diabetes

ALICIA JAWERBAUM

CANCUN

Congreso; 6th International Symposium on Metabolic Programming and Microbiome. 3rd Meeting of Ibero-American DOHaD chapter; 2018

Due to its crucial role in maternal-fetal interaction and fetal development, the placenta is a key organ in programming postnatal life. The relevance of the placenta in the extrauterine life has been demonstrated by the high number of programmed conditions associated with specific placental phenotypes. The placenta is highly involved in the induction of both intrauterine growth restriction and macrosomia, well known markers of adverse programming. Indeed, placental development and function are tightly coordinated with fetal development and closely interrelated to the genesis of adverse intrauterine programming. In many pregnancy complications, the placenta is involved in the generation of a prooxidant and proinflammatory intrauterine environment, which affects the proper placental function and thus fetal development. Oxidative stress is a hallmark in pregnancy diseases associated with adverse placental programming, including maternal diabetes, maternal obesity, undernutrition and hypertensive gestational pathologies. In our lab, markers of the prooxidant and proinflammatory state have been identified in the placenta of diabetic patients and experimental models of pregestational and gestational diabetes. These changes have been associated with a reduction in the levels and activity of the nuclear receptors PPARgamma and PPARalpha. PPARs are ligand activated transcription factors that regulate antioxidant, anti-inflammatory and metabolic functions, essential for embryo development and relevant to maintain a proper placental function. PPAR ligands have a lipid nature and include unsaturated fatty acids, which are rich in the olive, safflower and chia oils. In experimental models of pregestational diabetes, dietary supplementations with oils enriched in unsaturated fatty acids during pregnancy reduce placental oxidative stress and improve the placental function. As models of intrauterine programming, the offspring of pregestational diabetic rats show metabolic and cardiac alterations, and the female offspring of pregestational diabetic rats develop gestational diabetes (GDM). Rats with GDM show fetal macrosomia, an alteration related to the activation of mTOR pathways in the placenta. Treatments with PPAR agonists in the F0 generation prevent the prooxidant/proinflammatory state and the mTOR overactivation in the placenta of pregnant female offspring (F1 generation). Their capacity to exert antioxidant effects is similar to that of mitochondrial antioxidants, suggesting a potent antioxidant function of dietary PPAR agonists in maternal diabetes. These results point to oxidative stress as a relevant mechanism involved in intrauterine programming in maternal diabetes and highlight the ability of dietary treatments enriched in PPAR activators to target the placenta and ameliorate the impact of adverse intrauterine programming.