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.