Decreased leptin levels and leptin regulaton of nitric oxide levels in embryos from diabetic rats during early organogenesis

GONZÁLEZ ELIDA; WHITE VERÓNICA; CAPOBIANCO EVANGELINA; MARTÍNEZ NORA; HIGA ROMINA; JAWERBAUM ALICIA

Mykonos, Grecia

Congreso; Fourth Scientific Meeting, 37th Annual Meeting, Diabetes and Pregnancy Study Group. EASD; 2005

Diabetes and Pregnancy Study Group. EASD

Background: Mechanisms of induction of diabetic embryopathy are not completely understood. We previously found enhanced formation of nitric oxide (NO) and of the damaging agent peroxynitrite in embryos from diabetic rats. Leptin levels, closely related to insulinemia, are altered in serum and placental tissues from both diabetic women and experimental diabetic models. In addition, leptin regulates NO production in different tissues. As leptin is synthesized by the embryo, the aim of this work was to evaluate leptin levels and the effect of leptin on NO production in the embryos from diabetic rats during organogenesis. Methods: Embryos from control and diabetic rats (obtained through neonatal administration of streptozotocin, 90 mg/kg) were explanted on days 10.5 and 13.5 of gestation. Leptin levels were measured by EIA and immunohistochemistry. Embryos were cultured for three hours in the presence of leptin for further evaluation of NO production (by measurement of nitrites/nitrites, stable NO metabolites). Results: On day 13.5 of gestation leptin levels were decreased in embryos from diabetic rats (41%, p<0.05) when compared to controls. On day 10.5 of gestation leptin was not detectable by EIA, but a reduction in leptin levels in embryos from diabetic rats (60%, p<0.001) was observed by immunohistochemical analysis when compared to controls. The addition of leptin (1 nM) reduced the levels of nitrates/nitrites, stable NO metabolites, in embryos from control (36%, p<0.01) and diabetic rats (33%, p<0.01) on day 10.5 of gestation, and also in embryos from control (28%, p<0.05) and diabetic (36% p<0.01) rats on day 13.5 of gestation.  Conclusions: Leptin is a negative regulator of nitric oxide production during rat embryo organogenesis. In the embryos from diabetic rats, there is a reduction in embryonic leptin levels, an alteration probably involved in the high NO levels that lead to peroxynitrite formation and damage in diabetic embryopathy