Intrauterine growth restriction and impaired skeletal growth in mouse fetuses following maternal exposure to aflatoxin B1 during early and late organogenesis

Abstract

There is a paucity of information on the toxic effects of aflatoxins on reproduction, and any data that are available in the literature are largely from experiments with poorly described methodology, possibly making them unreliable. Consequently, the aim of this study was to evaluate the consequences of aflatoxin B1 (AFB1) administered during the early and late stages of organogenesis on fetal growth and development in the mouse. Groups of mice were administered a single dose of 20mg/kg AFB1 dissolved in dimethyl sulfoxide (DMSO) either intraperitoneally or orally on gestation day (GD) 7 or 13. The control animals received a similar volume of DMSO. Fetuses were collected on GD 18. This treatment was found to be maternally non-toxic; however, AFB1 treatment resulted in a significantly increased incidence of fetuses with intrauterine growth restriction, characterized by a body weight of ≥ 2 standard deviations below the mean of the control animals. A significant number of fetuses of AFB1-treated mice were also found to have developed smaller kidneys. In addition, the AFB1 group fetuses exhibited delayed ossification of the supraoccipital bone, cervical and coccygeal vertebral bodies, and the bones of the forepaws and hindpaws. Another major finding was a significantly increased incidence of cervical ribs and sternal anomalies. Interestingly, the effects of AFB1 were found to be more severely pronounced in the GD-13 treatment group than in the GD-7 treatment group. These results show that the later organogenesis stage of development (GD 13) is more susceptible to the deleterious effects of AFB1 in mouse fetuses.