Transplacental effects of endotoxemia on fetal mouse brain, bone, and placental tissue.

Pregnant mice were given 0.005 mg endotoxin on day 10 of gestation or 0.0025 mg endotoxin on days 10 and 12. Pregnant mice treated with normal saline served as controls. On day 18 of pregnancy, fetuses and placentas were removed for microscopic and histological examination. The treated placentas had fibrin thrombi and hemorrhages in the labyrinth and spongiosa. Glycogen cells in the spongiosa were swollen. The long bones of experimental animals had few metaphyseal trabeculae, which also were disorganized, with an increase in the number of metaphyseal and diaphyseal osteoclasts. An increase in the number of necrotic neurons was observed in coronal sections of brains of experimental fetuses at the level of the trigeminal ganglion. To correlate the degree of neuronal necrosis with long-term behavioral effects, a behavioral test was performed on pups whose mothers were treated with endotoxin. The pups were tested at the age of 28 days and for the next 3 days for their audiogenic seizure response. The pups of the experimental groups were more sensitive to high sounds than the controls. Escherichia coli endotoxins seemed to have a significant teratogenic effect on mice, being more severe when endotoxin was given in divided doses to the pregnant animals. The widespread endothelial damage or the elevation of prostaglandin levels caused by endotoxins may have been responsible for these teratogenic effects.