Developmental Abnormalities Due to Exposure of Mouse Paternal Germ Cells, Preimplantation Embryos, and Organogenic Embryos to Acrylamide

ABSTRACT The developmental toxicity of acrylamide was investigated after paternal germ cells and preimplantation and organogenic embryos were exposed to the agent. In the first experiment, ICR male mice were injected intraperitoneally with single doses of 62.5 or 125 mg/kg acrylamide or daily doses of 50 mg/kg for 5 days. They were mated with untreated virgin ICR female mice on days 1–21 and 64–80 after the last injection. The sperms involved in fertilization during these two periods were postmeiotic germ cells and spermatogonial stem cells, respectively, at the time of acrylamide treatment. The uterine contents were examined on day 18 of gestation for dominant lethal effects, and the fetuses were examined for external malformation. Acrylamide exposure during the postmeiotic cell or spermatogonial stem cell stage caused no significant increases in the incidence of abnormal fetuses. Dominant lethals, however, were clearly induced when the germ cells had been postmeiotic at the time of acrylamide exposure. In the second experiment, ICR mice were injected intraperitoneally with a single dose of 125 mg/kg acrylamide on day 0, 1, 2, or 3 of gestation. The uterine contents were examined on day 18 of gestation. Acrylamide treatment on day 0 of gestation caused a significant increase in the incidence of malformed fetuses, while treatment on day 1, 2, or 3 of gestation failed to cause an increase in malformation. Polydactyly was the most common type of abnormality. In the third experiment, pregnant mice were treated with three daily doses of 50 or 100 mg/kg acrylamide on days 6–8 or 9–11 of gestation, respectively. There was no significant difference between the incidence of malformed fetuses in the control and acrylamide-treated groups. These experiments demonstrate the vulnerability of preimplantation embryos to the toxic effects of acrylamide, while paternal germ cells and the organogenic embryos are resistant to the induction of fetal malformations.