Folate deficiency and congenital malformations induced by pyrimethamine in the rat.
In order to establish a relationship between the appearance of congenital malformations and the decrease of folic acid in rat mothers and embryos, a folic acid antagonist, pyrimethamine (PY), was administered. On the 12th day of gestation/pregnant rats received an intraperitoneal injection of 12.5, 15.63, 18.75 or 25 mg/kg PY. On the 13th day of gestation folic acid was measured in different maternal and embryonic tissues obtained after surgical hysterectomy of 1 uterine horn. On the 21st day of gestation malformations were studied on live fetuses remaining in the opposite horn. The folate levels were identical in all maternal tissues. The concentration of folic acid significantly decreased (50%) within the embryonic tissues in all PY-treated groups. A decrease of fetal weight occurred in the 18.75 and 25 mg/kg PY groups. Malformations were observed in the same groups. A dysfunction of the placental transfer of folates is hypothesized.
Raynaud
F
F
Laboratoire de Physiopathologie du Dévelopment, Université Pierre-et-Marie-Curie, Paris, France.
Horvàth
C
C
D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology*; D005260:Female; D005333:Fetus / Q000187:drug effects; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D005492:Folic Acid; D011739:Pyrimethamine