Transient inhibition of DNA synthesis by methotrexate, in the rat embryo and foetus

Massive doses of methotrexate, a folic acid inhibitor, followed by folinic acid, the specific antagonist, have been used to produce a period in which the embryo and foetus are exposed to tetrahydrofolate deficiency with subsequent inhibition of DNA synthesis. The effects of this inhibition vary at different stages of gestation, and in late foetal life provide a useful method of inducing a delay in the appearance of vertebral body ossification centres. This defect is rapidly repaired, although there may be permanent sequelae. It is hoped that this technique will be useful in the study of cellular events in ‘catch-up’ growth.