PPARdelta and its activator PGI2 are reduced in diabetic embryopathy: Involvement of PPARdelta activation in lipid metabolic and signaling pathways in rat embryo early organogenesis

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

MOLECULAR HUMAN REPRODUCTION.

W.B. SAUNDERS

Lugar: London, UK; Año: 2007 vol. 13 p. 103 - 110

1360-9947

Maternal diabetes significantly increases the risk of congenital malformations and the mechanisms involved are not yet clarified. This study was designed to address PPARd involvement in diabetic embryopathy. We investigated the concentrations of PPARd and its endogenous agonist PGI2, as well as the effect of PPARd activation on lipid metabolism and PGE2 concentrations in embryos from control and streptozotocin diabetic rats during early organogenesis. Embryos from diabetic rats showed decreased concentrations of PPARd and its endogenous agonist PGI2 when compared to controls. In embryos from control rats, the addition of the PPARd activators (cPGI2 and PGA1) increased embryonic phospholipid levels and de novo phospholipid synthesis studied using 14C-acetate as a tracer. PGE2 formed from arachidonate released from phospholipid stores was also upregulated by PPARd activators. In the embryos from diabetic rats, reduced phospholipid synthesis and PGE2 content were observed, and clearly upregulated by cPGI2 additions to values similar to those found in control embryos. These data suggest that PPARd may play an important role in lipid metabolic and signalling pathways during embryo organogenesis, developmental pathways that are altered in embryos from diabetic rats, possibly as a result of a reduction in levels of PPARd and its endogenous activator PGI2.