Induction of fetal malformations after treatment of mouse embryos with methylnitrosourea at the preimplantation stages.
The effects of methylnitrosourea (MNU) on the development of preimplantation mouse embryos were investigated in this study. ICR mice were treated intraperitoneally with single doses of 10, 20, and 30 mg MNU/kg body wt on day 0, 1, 2, or 3 of pregnancy. The uterine contents were examined on day 18 of pregnancy. The fetuses were examined for external and skeletal abnormalities. No significant differences were observed in the number of implantation sites between all the MNU-treated groups and controls. MNU treatment on day 2 or 3 of pregnancy caused dose-dependent significant increases in the incidence of abnormal fetuses over the control level, while treatment on day 0 or 1 failed to cause an increase of abnormalities. Cleft palate, exencephalus, and malformed vertebrae were the most common types of abnormalities. In the embryo transfer experiments, the frequency of fetal abnormalities induced when embryos were transferred from MNU-treated females to untreated pseudopregnant females was significantly higher than that induced when embryos were transferred from untreated females to MNU-treated or untreated pseudopregnant females. The results in the present study confirm and extend the previously proposed hypothesis that the direct effects of MNU on preimplantation embryos make a significant contribution to the induction of fetal malformations.
Department of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
T
T
Nagao
Y
Y
Morita
Y
Y
Ishizuka
A
A
Wada
M
M
Mizutani
D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013723:Teratogens
D013723:Teratogens; D008770:Methylnitrosourea