Yolk sac concentration of prostaglandin E₂ in diabetic pregnancy: Further clues to the etiology of diabetic embryopathy

Fetal malformation associated with maternal diabetes occurs before the seventh week of pregnancy. Current hypotheses suggest that the diabetic milieu causes a reduction in phosphatidylinositol turnover, leading to a disruption in the arachidonic acid cascade and resulting in a deficiency of prostaglandins, particularly prostaglandin E₂. This in turn results in a wide variety of congenital anomalies. This hypothesis has not been tested experimentally in humans. The yolk sac is thought to be the most important source of nutrition in early pregnancy. We sought to compare yolk sac prostaglandin levels in normal and diabetic women. Under ultrasonographic guidance, yolk sacs were aspirated from 8 normal and 12 diabetic women ranging from 8 to 10 weeks gestational age prior to elective abortion. Prostaglandin E₂ levels were determined using RIA. The mean prostaglandin E₂ level in normal controls was 3605 pg/mL, and was undetected in all of the yolk sacs aspirated from diabetic women (P < 0.001). Yolk sac diameter in diabetic pregnancies was 1.2 mm larger than that of normal pregnancies. The functional and morphological changes demonstrated in this study may increase our understanding of the pathophysiology of diabetic embryopathy.