Toxic effects of a single parenteral dose of tunicamycin in late stage pregnancy in rats.

Tunicamycin (TM) was given as a single parenteral dose at 3 levels to female rats at gestation day 15 (GD 15) and also to non-pregnant rats. At 16 h post-dosing all pregnant rats had moderate to extensive vaginal bleeding and 1/4 at each of the 2 higher doses died. The other severely affected rats, euthanized after 26-28 h, had free blood in the uterus and large decreases in red cell count (RCC), hemoglobin (Hb) and packed cell volume (PCV). The amnion of the fetuses was very easily detached from the maternal placenta by gentle manipulation. Histologically, hemorrhage, venous thrombosis and ischemic necrosis, particularly in the maternal placenta, were consistent with the gross appearance. There was no hemorrhage in any control pregnant rats. In the remaining TM-treated pregnant rats, euthanized at GD 17, there were lesser dose-related decreases in RCC, Hb and PCV, but there was no evidence of bleeding or changes in red blood cell parameters in non-pregnant rats. There was a dose-related decrease in cholesterol and GlcNAc-1-P transferase (GPT) activity and a treatment-related decrease in serum proteins in all rats. Maternal toxicity was demonstrated in pregnant rats at TM doses < 10% of a TM lethal dose in non-pregnant rats.