EFFECTS OF HYPERVITAMINOSIS A ON FETUSES OF bc STRAIN MICE WITH OBSERVATION OF THE INCIDENCE OF EXENCEPHALY COMPARED WITH ICR STRAIN MICE

Abstract

Hypervitaminosis A in gravid mice of the bc (experimental series I and II) and ICR (series III) strains was induced by daily subcutaneous injections of excess amount of vitamin A on 3 successive days during various early periods of gestation in view of causing various kinds of abnormalities, especially exencephaly, in fetuses. Autopsy was made on day 18 of gestation. Series I. Gravid bc strain mice were treated with 8,000-10,000 I.U. or 5,000 I.U. vitamin A once a day on days 8-10 of gestation. The daily dose of 8,000-10,000 I.U. caused fetal resorption and death in extremely high rates. On the other hand, 5,000 I.U. kept many fetuses alive and caused 100% abnormalities in living fetuses ; high incidence of micromelia, cleft palates and abnormal digits such as oligodactylia, syndactylia and abnormal directions were found. Other observed abnormalities were brachygnathia, short tail, open eyelids, microstomia and gastroschisis. In this series, no exencephaly was found. Series II. During various 3-day-periods including that of days 8-10, pregnant bc strain mice were treated with 2,500 or 5,000 I.U. vitamin A once a day. Treatments on days 8-10 caused a high incidence of cleft palates, micromelia and abnormal digits as observed in series I. Treatments on days earlier than these days and later than days 4-6 caused cleft palates in a high incidence and a case of open eyelids. No exencephaly was observed in this series as well. Series III. This series of experiments was conducted in view of strain-difference in the occurrence of exencephaly, an anomaly which was not observed in our colony of the bc strain though such anomaly seemed to appear in mice of the other strains heretofore reported, and in view of a high susceptibility of the ICR strain for exencephaly-causing activity of excess vitamin A (Ezaki 1964). Treatments were made on susceptible days for exencephaly, and resulted in the occurrence of exencephalies. The observed abnormalities were cleft palates, micromelia, oligodactylia, microtia, microcephaly, exencephaly, exophthalmos, open eyelids and short tail. The observed exencephalies reached a maximum incidence of 14% (7 cases) by treatments on days 6-8 with 10,000 I.U. vitamin A once a day. Furthermore, one case of exencephaly was found in a mother treated on days 8-10. The observations show that there exists a mouse strain (bc) which is not susceptible for exencephaly-causing activity of excess vitamin A.