Male-mediated teratogenesis: spectrum of congenital malformations in the offspring of A/J male mice treated with ethylnitrosourea.

Male mice of inbred strain A/J were intraperitoneally treated with ethylnitrosourea (ENU). On day 64-82 posttreatment, the males were mated with untreated virgin females of the same strain. Copulation involved sperm that were spermatogonial stem cells at the time of treatment. On day 18 of gestation, viable fetuses were inspected for external malformations. The most common malformation to occur spontaneously in the control group was cleft palate or cleft lip. Similarly, in the ENU-treated series, cleft palate or cleft lip was the predominant malformation, the frequency (15%) of which was significantly increased in the highest dose group (5 x 50 mg/kg) compared to control (8%). Based on these results and other data, we propose that a large fraction of external malformations in fetuses from mutagenized paternal germ cells are a result of increased yields of spontaneously occurring malformations.