Sex-related differences in procarbazine-induced cleft palate and microgenia and the anti-teratogenic effect of prenatal folic acid supplementation in rats.
Sex-related differences in the frequency of cleft palates and microgenia in rat fetuses prenatally treated with procarbazine (200 mg/kg on day 14 of gestation (GD14), group 1), and the anti-teratogenic effect of prenatal folic acid supplementation (4 mg/kg on GD14 through GD17, group 2) were studied in LEW.1A rats. In group 1, complete clefts were observed in 69% of the male and in 36% of the female fetuses while incomplete clefts (present only in the hard palate) were exhibited by 31% of the males and 43% of the females. Microgenia occurred in all males but only in 64% of the female fetuses. In group 2, the prenatal folic acid supplementation significantly reduced the occurrence frequency of complete clefts to 9% in males and to 0% in females. In contrast, incomplete clefts increased to 82% in males and 91% in females. Microgenias were reduced to 73% and 57% in male and female fetuses, respectively. Since incomplete clefts present in the hard palate are assumed to be residues of spontaneous intra-uterine repair processes of exogenously induced complete palatal clefts, we conclude that prenatal supplementation with folic acid at a dose of 4 mg/kg promotes the intra-uterine repair of cleft palates and offers a partial protection against procarbazine teratogenicity. Furthermore, it is deduced that gender-specific differences exist in the susceptibility to procarbazine and in the anti-teratogenic effect of folic acid on procarbazine-induced microgenia.
Department of Anatomy, Ernst Moritz Arndt University, Friedrich-Loeffler-Strasse 23 c, D-17487 Greifswald, Germany.
F A
FA
Malek
K U
KU
Möritz
J
J
Fanghänel
V
V
Bienengräber
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D000013:Congenital Abnormalities / Q000517:prevention & control; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D011247:Pregnancy; D011344:Procarbazine / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics; D013723:Teratogens
D013723:Teratogens; D011344:Procarbazine; D005492:Folic Acid