Abstract 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 References 1. Nelson, M. M., and Evans, H. M.: Pteroylglutamic Acid and Reproduction in the Rat , J. Nutrition 38:11, 1949. 2. Thiersch, J. B., and Philips, F. S.: Effect of 4-Amino-Pteroylglutamic Acid (Aminopterin) on Early Pregnancy , Proc. Soc. Exper. Biol. & Med. 74:204, 1950. 3. Giroud, A., and Lefebvres-Boisselot, J.: Influence tératogène de la carence en acide folique , Compt. rend. Soc. biol. 145:526, 1951. 4. Nelson, M. M.; Asling, C. W., and Evans, H. M.: Production of Multiple Congenital Abnormalities in Young by Maternal Pteroylglutamic Acid Deficiency During Gestation , J. Nutrition 48:61, 1952. 5. Thiersch, J. B.: Therapeutic Abortions with a Folic Acid Antagonist, 4-Aminopteroylglutamic Acid (4-Amino P. G. A.) Administered by the Oral Route , Am. J. Obst. & Gynec. 63:1298, 1952. 6. Thiersch, J. B.: The Control of Reproduction in Rats with the Aid of Antimetabolites and Early Experiments with Antimetabolites as Abortifacient Agents in Man , Acta Endocrinol. ( (Supp. 28) ) 23:37, 1956. 7. Meltzer, H. J.: Congenital Anomalies Due to Attempted Abortion with 4-Aminopteroglutamic Acid , J. A. M. A. 161:1253, 1956. 8. Apgar, V.: A Proposal for a New Method of Evaluation of the Newborn Infant , Anesth. & Analg. 32:260, 1953. 9. Patten, B. M.: Human Embryology , Ed. 2, New York, The Blakiston Company (division of McGraw-Hill Book Company, Inc.), 1953. 10. Whitehouse, D. B., and McKeown, T.: A Note on the Significance of Attempted Abortion in the Aetiology of Congenital Abnormalities , J. Obst. & Gynaec. Brit. Emp. 63:224, 1956. 11. Warkany, J.: Can the Origin of Congenital Malformations Be Dated by Their Morphological Characteristics? A. M. A. J. Dis. Child . 94:434, 1957. 12. Gruenwald, P.: Malformations Caused by Necrosis in the Embryo: Illustrated by the Effect of Selenium Compounds on Chick Embryos , Am. J. Path. 34:77, 1958. 13. Fulton, J. T.: Closure of the Human Palate in Embryo , Am. J. Obst. & Gynec. 74:179, 1957. 14. Streeter, G. L.: Development of the Auricle in the Human Embryo , in Carnegie Contributions to Embryology , Vol. 14, Washington, D. C., Carnegie Institution of Washington, 1922, p. 111.
A.M.A. Journal of Diseases of Children – American Medical Association
Published: Mar 1, 1959