Diminished levels of prostaglandin E in type I diabetic oocyte–cumulus complexes. Influence of nitric oxide and superoxide dismutase

Abstract

In the present work the prostaglandin E (PGE) production by ovulated, immature and in vitromatured oocyte–cumulus complexes (OCC) was evaluated in a rat model of type I diabetes induced by streptozotocin (60 mg kg^–1). A diminished number of ovulated OCC were found in the type I diabetic rat. In contrast to the increment in PGE generation found previously in OCC and embryos from type II diabetic rats, it was found that PGE production by type I diabetic OCC was diminished in comparison with the controls. Nitric oxide synthase (NOS) activity is enhanced in proestrous ovaries from type I diabetic rats, but cGMP levels are diminished. SIN-1 (300 µМ), a nitric oxide donor, significantly enhanced PGE generation by control OCC, but was unable to modify the PGE levels in type I diabetic OCC. L-NMMA, a nitric oxide inhibitor that diminished PGE values in type II diabetic OCC, did not modify PGE generation in either control and type I diabetic OCC. Superoxide dismutase (SOD, 1000 U mL^–1), and SOD (1000 U mL^–1) plus SIN-1 (300 µМ), enhanced PGE generation by both control and diabetic OCC. The present results suggest that even when nitric oxide (NO) is overproduced in diabetic ovaries, the NO–PGE pathway is impaired in type I diabetic OCC. As SOD additions are able to increase PGE generation by diabetic OCC, high concentrations of free oxygen radicals might be quenching the NO, impairing its physiological functions.