Frequency and Type of Malformations in the Offspring of C57BL/6 Male Mice Treated with Ethylnitrosourea

Male mice of inbred strain C57BL/6 were intraperitoneally treated with ethylnitrosourea (ENU). On days 64–80 after the treatment, the males were mated with untreated virgin females of the same strain and allowed to utilize sperm that were spermatogonial stem cells at the time of treatment. On day 18 of gestation, viable fetuses were inspected for external malformations. The frequency of externally malformed fetuses in the ENU‐treated series increased significantly over the control level. Malformations occurred spontaneously in the control series were microphthalmia and micrognathia. In the ENU‐treated series as well, they occurred and no other malformations were encountered. The frequencies among total malformations of microphthalmia were 95% and 92% in the control and the ENU‐treated series, respectively. Based on these results and other data, we propose that the male‐mediated teratogenesis represents spontaneous teratogenesis that is enhanced over the normal level by paternally transmitted germ‐line mutation(s).