Basic Science and the Placenta Symposium Session. Charla titulada: "Altered pro-inflammatory and anti-inflammatory pathways in embryos and placenta from diabetic pregnancies

JAWERBAUM

Estambul, Turquía

Simposio; 4th International Symposium on Diabetes and Pregnancy; 2007

International Association of Diabetes and Pregnancy

In maternal diabetes, developmental anomalies in the embryo and the placenta may arise from exposure to a pro-inflammatory environment. Our studies show an overproduction of several pro-inflammatory agents in the embryo and placenta from experimental models of diabetes, as well as in placenta from diabetic women. Embryos from diabetic experimental models explanted during early organogenesis, a highly suceptible period for induction of malformations, show increased nitric oxide (NO) and reactive oxygen species (ROS), which lead to the formation of peroxynitrites, powerful oxidant and damaging agents. These embryos also show alterations in the levels of prostaglandins involved in neural tube closure, anti-inflammatory processes, and activation of the nuclear receptors PPARs. Propagation of the inflammatory procesess due to an impaired balance of pro-inflammatory/ anti-inflammatory agents is also found both in the feto-placental unit from diabetic rats and in human diabetic placenta. In these diabetic tissues, increased NO, ROS and peroxynitrites lead to the overactivation of the proteolytic enzymes matrix metalloproteinases. Anti-inflammatory effects can be achieved by activation of nuclear receptors PPARs in the feto-placental unit, but there are alterations in the levels of both PPARs and their endogenous agonists in both fetuses and placenta from diabetic mothers. Collectively, the impaired pro-inflammatory/anti-inflammatory pathways may threaten the developmental processes throughout diabetic gestations, inducing loss of the needed stringent control during development and exerting direct damage to both the embryo and the placenta.