DIABETES-MELLITUS AFFECTS PROSTAGLANDIN E(2) LEVELS IN MOUSE EMBRYOS DURING NEURULATION

The arachidonic acid cascade leading to prostaglandins has been implic ated in diabetic embryopathy Both arachidonic acid and prostaglandin E (2) reverse the teratogenic effects of high glucose concentrations on neural tube development in mouse embryos in culture. Arachidonic acid supplementation also protects against diabetes-induced neural tube def ects in vivo. In the present study, prostaglandin E(2) was measured di rectly in embryos from normal and diabetic mice. In normal mice a clea r developmental pattern was seen. Prostaglandin E(2) levels were high during early formation of the cranial neural folds (day 8), declined d uring convergence and fusion of the cranial neural folds to form the n eural tube (day 9), and were low after neurulation was complete (days 10 and 11). In addition, evidence in this study indicates that embryos have cyclooxygenase activity capable of generating prostaglandin E(2) during a brief developmental period preceding neural tube closure. In embryos from mice made diabetic (> 13.9 mmol/l glucose) with streptoz otocin, prostaglandin E(2) levels were significantly lower than normal during early development of the cranial neural folds (day 8), but sim ilar to normal after the cranial neural tube had closed (late day 9 an d day 10). The findings suggest that diabetes mellitus, as ascertained by high blood glucose, promotes cranial neural tube malformations by causing a functional deficiency of prostaglandin E(2) during early neu rulation. Whether the altered PGE(2) pattern in the embryo indicates a diabetic effect on the arachidonic acid-prostaglandin cascade in cell s of the embryo or in cells of extraembryonic or maternal tissues is u ncertain.