Effects of amethopterin (methotrexate) on the evolution of pregnancy in rats.

Amethopterin (4-amino-N-10-methyl-glutamic acid) was given to pregnant rats in varying doses at different periods of gestation to evaluate its effects upon both the mother and the fetoplacental unit. The maternal organism is more sensitive to this drug at days 14 to 17 than at a larger stage of gestation. When administered to rats from day 14 to day 18 of pregnancy the drug is capable of inducing a series of deleterious effects: maternal weight loss, resorption, abortion or hypotrophy of fetuses. Day 16 appears to be a critical moment in the evolution of rat pregnancy, after which injection of amethopterin does no longer impair fetoplacental growth. Before this date, the drug directly inhibits fetal weight gain, whereas the sensitivity of the placenta is only transient at day 16 resulting in maximum weight decrease of this organ 24 h later. Its action on rat pregnancy follows a direct dose-effect relationship reflecting increasing damage to the products of conception (resorption, abortion and hypotrophy).