Question: The drug methotrexate has been reported to cause fetal death and/or congenital anomalies, therefore, it is not recommended for women of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks. Why do you suspect that methotrexate is so dangerous to a growing fetus?

A lack of PRPP would prevent both the de novo and salvage pathways of purine biosynthesis.

Inactive RNA polymerase is incompatible with life.

Orotic aciduria in the mother is deadly to the fetus.

Rapidly dividing cells need a lot of dTMP.

Without base excision repair, even a growing fetus will age too rapidly