EXPOSURE TO ETHYLENE-OXIDE DURING THE EARLY ZYGOTIC PERIOD INDUCES SKELETAL ANOMALIES IN MOUSE FETUSES

Exposure of mouse zygotes to ethylene oxide (EtO) has been shown to in crease the incidence of external malformations among late fetuses [Gen eroso et al. (1987) Mutat. Res., 176:267-274; Rutledge and Generoso, ( 1989) Teratology, 39:563-572]. The present study was designed to deter mine whether EtO also affects the skeletal system. We report here the effects of varying times of exposure during the zygotic period on skel etal development. Female hybrid mice were injected intraperitoneally ( IF) with 125 mg/kg EtO at 1, 3, 5, or 7 hr postmating. A positive cont rol group consisted of female mice that were injected IP with 150 mg/k g EtO once daily between the 6th to 8th days of gestation. Day 17 fetu ses were double-stained for ''blind'' examination of skeletal deviatio ns and degree of ossification. Zygotic exposure to EtO significantly i ncreased loss of conceptuses as well as the incidence of external defe cts, skeletal anomalies, and retarded ossification in live day 17 fetu ses. An increase in the number of exposed fetuses with cleft sternum w as observed with the highest rate (58.5%) occurring in fetuses whose m others were exposed to EtO 3 hours postmating. Cleft sternum was seen in only 5% of fetuses exposed during the period of organogenesis and l ess than 1% of control fetuses. It is concluded that zygotic exposure to EtO produces a pattern of skeletal defects that differs from those observed following treatment with EtO during organogenesis. (C) 1996 W iley-Liss, Inc.