The limb buds and foot plates of Pdn mouse embryos were examined with cartilage-stained cleared specimens, histological sections and vital-stained specimens with Nile blue A. The homozygotes could be distinguished by the external features of the foot plate from day 12 of gestation and the heterozygotes from day 14. The chondrogenesis of extra-digits could be observed as well as the normal digits on day 14 of gestation in the homozygotes. Histologically, the involution of the apical ectodermal ridge in homozygotes was delayed at the preaxial portion, as were the mesodermal condensations of digital blastema of the extra-digits. The normal patterns of physiological cell death in the apical ectodermal ridge, the deep preaxial mesoderm and preaxial marginal mesoderm were disrupted in the homozygotes. The results suggested that an absence of physiological cell death might play a significant role in the production of the preaxial polydactyly.

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The effects of an antipsychotic drug, haloperidol, which is known to induce delayed implantation, on mouse preimplantation development were investigated. Ovulation was not affected when haloperidol was injected into female mice after copulation and shortly before ovulation. The first, second and third cleavages and the blastocele formation were significantly delayed in ova from mice receiving a serial subcutaneous injection of haloperidol at 24-hour intervals from shortly before ovulation. The delay tended to become longer with subsequent cleavages. The first three cleavages were also significantly delayed in ova from mice given a single subcutaneous injection of haloperidol shortly before ovulation. When the haloperidol was injected at the time when most ova were conjectured to have been penetrated by spermatozoa, the first cleavage was not delayed, but the time for more than 25% of the ova to undergo the second and third cleavages was significantly delayed. When haloperidol was injected at the tirne corresponding roughly to the 2- or 4-cell stage of ova, the second and third cleavages were not delayed. The earlier the injection with haloperidol, the greater was the cleavage delay. The possible mechanisms involved in the delay of implantation and cleavages were discussed.

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Administration of pregnant rats with cytosine arabinoside (ara-C) on day 11 produced preaxial polydactyly (87.9%) and on day 12 or 13 led to oligodactyly formation (day 12, 57.3%; day 13, 86.8%) in the hindlimb. However, the repeated treatments on 2 days 11 and 12 or 11 and 13 not only converted the polydactyly-inducing effect into the oligodactyly-inducing effect, but also reduced (49.2%, on days 11 and 12) or increased (100%, on days 11 and 13) the incidence of total digital malformations compared with that of single treatment on day 11, 12 or 13. This outcome might be due to the different susceptibility of the ectodermal and the mesodermal cells to the teratogen, because the stage of cellular differentiation was found to be different between the ectoderm and the mesoderm of the hindlimb bud. Although digital malformations produced by repeated treatments show more complex features than those produced by a single treatment, such experiments might be helpful to understand the pathogenesis of human digital malformations which are often too complex to be classified.

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Twelve Chinese harnsters with reciprocal translocations were obtained among 118 offspring from 97 crosses between X-irradiated males and non-irradiated females. Eleven were fertile, but one male with a t(Y ;1) translocation was sterile. Among the offspring of fertile animals, male heterozygotes for a t(X ; 1) translocation were also sterile, whereas female heterozygotes for the same translocation were fertile. By intercrossing heterozygotes, four stocks homozygous for a reciprocal translocation were established.

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Thalidomide was administered orally at a dose level of 300 mg/kg to pregnant rabbits on various days during organogenesis. Various cranio-facial malformations were produced in the fetuses by treatment on days 6-11 of gestation, such as anencephaly, holoprosencephaly, dysgenetic hydrocephaly, hypoplasia of ala nasi, facial median cleft, cleft palate and microphthalmia. No external anomalies were observed from treatment on days 12-18 of gestation. Single administration of thalidomide from days 6 to 8 of gestation resulted in a greater incidence of cranio-facial malformations, especially from treatment on day 7. To study the morphogenetic process, the fetuses were observed histologically on days 10-16 of gestation. The telencephalic wall was everted at the midfrontal line in the 11 -day fetus, and the eversion became more remarkable with the fetal developmental stage.

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A warning was issued to the use of the Mann-Whitney U test (or Wilcoxson's sum rank test) in teratological or pre-clinical studies with many ties. The limitation of the U test was exemplified by a computer simulation experiment. A probable situation in teratological or pre-clinical studies, in which grave error might be caused by the employment of erroneous significance criteria was discuss-ed.

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