Pteroylglutamic acid (PGA, folic acid) plays an important role in many biological reactions, and PGA deficiency may lead to death of mammalian embryos. Nelson and Evans1 demonstrated reproductive failure in rats kept on a PGA-deficient diet containing succinylsulfathiazole and a crude PGA antagonist. Thiersch and Philips2 induced fetal death in rodents kept on an adequate diet by administration of aminopterin (4-amino-pteroylglutamic acid), a powerful PGA antagonist. Later Giroud and Lefebvres-Boisselot3 and Nelson, Asling, and Evans4 produced multiple congenital abnormalities by maternal PGA deficiencies during gestation.
Aminopterin has also been used to induce therapeutic abortions in women with tuberculosis or cancer. In 10 out of 12 cases reported by Thiersch5 oral doses of 6 to 12 mg. aminopterin induced fetal death in the first trimester of pregnancy, followed by spontaneous delivery of the products of conception. The doses lethal to the embryo had only mild effects