Early effects of ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats and mice

The industrial chemical 4-vinylcyclohexene diepoxide (VCD) causes specific destruction of oocyte-containing small preantral follicles (primordial and primary) in ovaries of rats and mice, The mouse seems more susceptible to o votoxic effects of VCD than the rat. The purpose of this study was to bette r understand these species differences in susceptibility to VCD by comparin g the initial rates of VCD-induced follicle damage and loss in response to dosing in both species, Female Fischer 344 rats and B6C3F1 mice (age, Day 2 8) were dosed daily (vehicle or 80 mg/kg, i.p.) for 6, 8, 10, or 12 d, Ovar ies collected after the final dose were prepared for histologic evaluation, Primordial and primary follicles in ovarian slices were counted and classi fied as healthy or atretic, A VCD-dependent increase (P < 0.05) in percent atretic primordial follicles was first observed 4 h after the final dose in mice on Day 8 (VCD-treated, 44.4 +/- 3.1% vs, control, 26.9 a 5.4%). Conve rsely, in rats, this significant increase was not seen until Day 10 (VCD-tr eated, 44.3 a 1.3% vs. control, 23.1 a 4.0%). A VCD-dependent increase in p ercent atretic primary follicles was not observed in either species before Day 12, There was no significant effect on growing or preantral follicles o n any day in either species. Significant loss of primordial and primary fol licles (P < 0.05) was first measured on day 12 in both rats and mice. Howev er, when compared with controls, follicle loss on that day was greater (P < 0.05) in mice (64.2 +/- 4.5%) than in rats (34.7 +/- 4.9%), Once VCD-depen dent follicle loss was observed, the rate of follicle damage was similar in rats and mice, and was fairly constant in response to each dose. VCD-induc ed follicle damage in mice, as with rats, also displayed morphologic charac teristics of atresia (apoptosis). In summary, follicle destruction seems to be similar in rats and mice; however, follicle damage is initiated earlier and to a greater extent in mice than in rats, Additionally, ovotoxic effec ts of VCD seem to initially directly target primordial follicles, These res ults provide temporal evidence that mice are more susceptible to VCD-induce d ovotoxicity than rats. (C) 1999 Elsevier Science Inc.