Is compensatory growth a complicating factor in mouse teratology?

Abstract

METHODS developed in an attempt to optimise the chances of identifying a teratogen generally involve the administration of the compound to a pregnant female in a number of ways, followed by autopsy about 24 h before parturition. This system maximises the period during which abnormalities may develop and circumvents loss by cannibalisation of dead or deformed newborn animals by their mother. The methodology is simple and efficient but provides no information about the immediate response of the embryo to the drug and any capability it may have for regulation or recovery from damage. Thus developmental disturbances could pass unnoticed. However, the damage, for example behavioural or reproductive abnormality, may manifest itself postnatally, and this has recently aroused some concern^1,2. We report here on the mode of action of a known teratogen, mitomycin C (MMC) on mouse embryos. In rodents this antibiotic is teratogenic at high doses. In rats the LD₅₀ and teratogenic dose seem to coincide, but for mice these figures may differ considerably^3–5. Abnormalities reported include exencephaly, spina bifida⁶, skeletal and other non-nervous system defects⁷. The frequency of abnormality and dose response is strain dependent in mice. We know of no reports on the immediate response of mouse embryos to MMC and of only one on the postnatal development of mice exposed to the drug in utero in mid-gestation⁸. Our results indicate that, during early organogenesis stages, the mouse embryo has a remarkable capacity for recovery from severe damage and developmental retardation induced during primitive-streak stages, when drugs were thought more likely to be lethal than teratogenic.