Multiple Congenital Abnormalities Resulting from Transitory Deficiency of Pteroylglutamic Acid during Gestation in the Rat

Abstract

Multiple congenital abnormalities have been produced in the rat by an extremely short and transitory deficiency of pteroylglutamic acid instituted during the early part of pregnancy, the “critical” period of differentiation and organogenesis. A deficiency period of only 48 hours during this period, after implantation on day 7 and before day 12, resulted in 70 to 100% abnormal young or fetal death. In contrast a 24-hour period of deficiency after implantation had practically no effect on fetal development nor did a 72-hour deficiency period before implantation. The earlier phases of embryonic development were more severely affected by the same length of deficiency than the later phases. Throughout the experiments the mothers receiving the PGA-deficient diet gained weight and were in good condition, regardless of death or abnormality of the fetuses. The abnormalities produced included multiple types of defects of the nervous, ocular, skeletal, respiratory, cardiovascular, and urogenital systems; the diaphragm and body walls were also affected. The type of anomaly and the incidence varied both with the duration and with the time of instituting the deficiency.