A dose-finding study of in utero and lactational exposure to diethylstilboestrol and flutamide in 129/Sv mice.
The purpose of the study was to test the experimental conditions and find the appropriate dose range for further investigations of the disruptive effects of oestrogens and antiandrogens on the development of testis. Groups of four 129/Sv mice were exposed from day 6 after mating until weaning to 1, 10 or 100 microg/kg/day of the non-steroidal oestrogen diethylstilboestrol and to 0.1, 1 or 10 mg/kg/day of the non-steroidal antiandrogen flutamide. The number of implantation sites, the litter size and reproductive parameters were examined and nipple development, anogenital distance and testicular morphology were investigated in the offspring. Dose-related post-implantation loss was seen in both diethylstilboestrol- and flutamide-treated dams and the mean litter size was smaller in the groups given the high dosages of diethylstilboestrol and flutamide. Disturbance of testicular development was seen in males exposed to diethylstilboestrol. Because of the small data material, no statistical analyses were performed. Our findings indicate that very high doses of both diethylstilboestrol and flutamide given at early stages of gestation result in a high post-implantation loss and should be avoided in further experiments using this strain which is known to have a poor reproductive performance. Exposure of the dams before mating may better reflect human exposure, but will presumably require even lower dose levels.
Kledal
T J
TJ
Department of Growth and Reproduction, University Hospital, Rigshospitalet, Copenhagen, Denmark.
Rajpert-De Meyts
E
E
Skakkebaek
N E
NE
Jørgensen
K D
KD
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005262:Feminization / Q000139:chemically induced / Q000196:embryology; D005485:Flutamide / Q000008:administration & dosage / Q000633:toxicity*; D007774:Lactation; D008098:Litter Size; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D013737:Testis / Q000187:drug effects* / Q000196:embryology
D000726:Androgen Antagonists; D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol; D005485:Flutamide