Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
Azathioprine are clinically used for the therapy of immunosuppression, but there are some reports which revealed embryolethality and teratogenic potentials in experimental animals. Last year, we reported there were embryolethality but no evidences which showed teratogenic potential by administration of this compound for 3 consecutive days for the organogenesis period in rats. In this present study, azathioprine was administered to pregnant rats with higher dose on each day for the organogenesis period to examine to maternal and developmental toxicities.
Sprague-Dawley female rats were orally administered to the compound once on each gestational days (GD) of 7 to 14, and maternal rats were examined for physical signs and weighed body weights. On GD 21, maternal rats were caesarian-sectioned and reproductive status were examined. Live fetuses were weighed and examined for external and skeletal abnormalities.
There were no effects on maternal physical signs, and temporal decreases in maternal body weight were observed the next day of treatment. Percent of postimplantation losses were markedly increased in treatment on each GD 7, 8, 9 or 10 (100%, 100%, 85.4% or 100%, respectively). Live fetal weights were slightly decreased in treatment on GD 9 or 11. There were no treatment-related external and skeletal abnormalities in any treatment days.
In conclusion, there were embryonic deaths and decreased fetal weights but were no evidences of teratogenic potentials, and the results were similar to those in the previous our study. Furthermore, the critical period for embryolethality was determined as GD 7 to 10 under the condition of this study.
