ABSTRACT The heterozygotes of Oligosyndactyly (0s) gene manifest syndactyly on fore- and hindfeet and sometimes axial oligodactyly in mice. 5-Fluorouracil (5-FU) is known to produce various types of digital malformations in mice. The present experiment was designed to examine possible interactions of 0s gene and 5-FU in the induction of digital malformations in mice. Female S1c:ICR mice were mated with Fi males (Os/ + or + / +) which were obtained from the cross between female ICR and male C57BL-Os/ + mice. Pregnant females were treated with a single intraperitoneal injection of teratogenic dose (20 mg/kg) or marginal teratogenic dose (10,7.5 and 15 mg/kg) on day 9, 10 and 11 of gestation, respectively. On day 17 or 18 of gestation, fetuses of treated and non-treated control groups were examined externally and in bone and cartilage double-stained specimens. The teratogenic dose of 5-FU increased the expressivity of 0s gene and, in turn, 0s gene caused an increased severity of 5-FU-induced postaxial oligodactyly. The interaction between 0s gene and marginal teratogenic dose of 5-FU varied according to the time of treatment. Increased expressivity of 0s gene could be observed in the groups treated with the marginal teratogenic dose of 5-FU on day 10 and day 11.
ABSTRACT The relationship between pyrimethamine (PYR) teratogenesis and the plasma level of 5-methyltetrahydrofolic acid (SMF), known as an active form of folate in plasma, was studied in rats using an HPLC-ECD method for 5MF determination. The rat received, for 5 days, in-feed PYR with or without folic acid (FA), which was previously reported as a potentiator of PYR teratogenesis. PYR alone caused a dose-dependent decrease in the plasma 5MF level after the 5 day dosings. A potentiated decrease in the 5MF level was observed after the concomitant dosing of PYR with FA. The concomitant dosing of PYR 1.6 mg/kgBW/day (subteratogenic dose of PYR alone) with FA 50 mg/kg/day, which was 100 Vo teratogenic dose in our previous report, decreased the 5MF level more than that after the dosing of PYR 3.6 mg/kg/day alone (100 Vo terato- genic dose of PYR alone). The sequential changes of the plasma 5MF level after the single oral dosing of PYR 3.6 mg/kg with or without oral FA 50 mg/kg also revealed a strong potentiative effect of oral FA on the SMF-level-lowering effect of PYR. These results indicate that a decrease in the plasma 5MF level may be related to PYR teratogenesis.
ABSTRACT Pregnant Wistar rats were given a single i.p. injection of 30 mg/kg ethylenethiourea (ETU) on one of gestational days 8.5 to 20.5. After rearing to postnatal day 20, the offspring were sacrificed and their brains were excised. Numerous brains removed from the pups prenatally treated with ETU on any day from gestational days 12.5 to 20.5 showed dilatation of lateral ventricle in various degrees. Histological ex- amination revealed forking and stenosis of third ventricle in these brains. Since the degree of the third-ventricular stenosis roughly corresponded to the degree of dilatation of lateral ventricle, this anomaly is considered to be the main cause of congenital hydrocephalus induced in rats by prenatal ETU-treatment. The embryological study showed that the ependymal lining of the third ventricle was partially denuded in the fetuses 24-48 hours after ETU-treatment , and also that the denuded ependymal lining was never repaired during the following gestational days; instead, the ventricular walls fused laterally in the area where the ependymal lining had been denuded.
ABSTRACT The effects of maternal exposure to 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen) on prenatal lung growth were examined by dietary administration (2,000 ppm in ICR mice and 500 ppm in CD rats). Embryos and/or fetuses (conceptuses) were re- moved from dams on days 12 to 18 of gestation in mice and on days 14 to 20 of gestation in rats. Body and lung weights of the conceptuses were measured. General growth retardation was noted especially in the later period of intrauterine life in both mice and rats. Bilateral retardation of lung development of the nitrofen exposed conceptuses was noticed throughout intrauterine life including the periods before the closure of pleuroperitoneal canals in both species indicating that nitrofen induced primary lung hypoplasia. In mice, the left lung was more hypoplastic than the right one, while it was opposite in rats. The species specificity in side prevalence of the developmental retardation of the lung was observed even before completion of the embryonic diaphragm and it was well in accord with the side on which posterolateral diaphragmatic hernia (Bochdalek's diaphragmatic hernia, BDH) took place later. We conclude that nitrofen induces primary lung hypoplasia regardless of the presence or absence of BDH.
ABSTRACT When the degree of skeletal ossification and the incidence of skeletal variations were compared between male and female fetuses in mice according to body weight, males had more ossification centers in sternebrae than did females, while ossification of thoracic and sacrococcygeal vertebral bodies tended to be more advanced in females. Also, more rudimentary ribs tended to appear in females and more extra ribs appeared in males.