Abstract
ABSTRACT Treatment of mouse preimplantation embryos with adriamycin (ADM), methyl methanesulfonate (MMS) and all‐trans retinoic acid (RA) on their later development including implantation, growth and organogenesis were investigated. ICR mice were treated intraperitoneally with ADM or MMS on day 3 of gestation, or with RA on day 4 of gestation. The uterine contents were examined on day 18 of gestation. The viable fetuses were inspected for external and skeletal malformations. Irrespective of the kind of chemical agents tested, frequencies of total malformed fetuses were significantly increased, whereas the frequencies were considerably lower than those of malformations in fetuses of dams treated with ADM, MMS or RA during the period of organogenesis. In the fetuses of ADM‐treated mice, the most common abnormality was umbilical hernia, followed by cleft palate. In the MMS‐treated fetuses, the most common abnormality was cleft palate. Among the malformations observed in this study, duplication of hindlimb (5/193 fetuses) induced by the treatment with RA at the preimplantation stage was a quite unique abnormality. This type of malformation has never before been found in our historical control embryos and in embryos treated with various kind of teratogens. Based on these results and other data, it is concluded that embryos at the preimplantation stage are susceptible to environmental chemical‐induced congenital malformations.
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