The role of alterations in arachidonic acid metabolism and nitric oxide homeostasis in rat models of diabetes during early pregnancy.
The diabetic pathology induces reproductive abnormalities that enhance spontaneous abortion, congenital anomalies and neonatal morbidity/mortality rates, abnormalities that begin with an altered female gamete. In this review we focus on the damage induced by maternal hyperglycemia during ovulation, early embryo development, implantation and embryo organogenesis in experimental rat models of diabetes. Hyperglycemia can induce cellular damage by enhancing the production of reactive oxygen species (ROS), by altering arachidonic acid metabolism (thus leading to altered production of prostaglandins such us PGE(2)and 15deoxydelta(12-14)PGJ(2), involved in signalling and developmental pathways), and by enhancing the generation of nitric oxide (a mediator of many cell functions including apoptotic cell death). In maternal diabetes all of these abnormalities are present from the oocyte stage, during embryonic implantation, and during embryo organogenesis. The involvement of these alterations in embryo loss and congenital malformations due to diabetes and the cross-talk among these metabolic pathways are discussed. As maternal hyperglycemia induces damage from the oocyte stage and throughout embryo development the data reviewed suggests the need of strict preconceptional metabolic control. The importance of the molecules involved in hyperglycemia-induced damage as future pharmacological targets for intervention is discussed.
Jawerbaum
A
A
Laboratory of Reproduction and Metabolism, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, (1414) Buenos Aires, Argentina. a.jawerbaum@abaconet.com.ar
Gonzalez
E
E
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats
D016718:Arachidonic Acid; D009569:Nitric Oxide