Early pregnancy failure induced by dibutyltin dichloride in mice.
In this study, we examined the adverse effects of dibutyltin on initiation and maintenance of pregnancy after maternal administration during early pregnancy in mice. Following successful mating, female ICR mice were given dibutyltin dichloride (DBTCl) at 0, 7.6, 15.2, or 30.4 mg/kg bw/day by gastric intubation on days 0-3 or days 4-7 of pregnancy. Female mice were sacrificed on day 18 of pregnancy, and the pregnancy outcome was determined. After administration of DBTCl on days 0-3, the rate of nonpregnant females and the incidence of preimplantation embryonic loss were significantly increased at 30.4 mg/kg bw/day. The incidences of postimplantation embryonic loss in females given DBTCl on days 0-3 at 15.2 mg/kg and higher and on days 4-7 at 7.6 mg/kg bw/day and higher were increased. No increase in the incidence of fetuses with external malformations was observed after the administration of DBTCl on days 0-3 or days 4-7. A decline in the serum progesterone levels was detected in mice given DBTCl at 30.4 mg/kg bw/day on days 0-3 or days 4-7 of pregnancy. The data show that DBTCl adversely affects the initiation and maintenance of pregnancy when administered during early pregnancy in mice and suggest that the decline in serum progesterone levels is responsible for pregnancy failure.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, Tokyo 185-8501, Japan. ema@nihs.go.jp
Fujii
Sakiko
S
Ikka
Tsuguo
T
Matsumoto
Mariko
M
Hirose
Akihiko
A
Kamata
Eiichi
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss / Q000139:chemically induced*; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011255:Pregnancy Maintenance / Q000187:drug effects*; D011261:Pregnancy Trimester, First; D011270:Pregnancy, Animal / Q000187:drug effects*; D011374:Progesterone / Q000097:blood; D013997:Time Factors
D007166:Immunosuppressive Agents; D009947:Organotin Compounds; D011374:Progesterone; C020735:dibutyldichlorotin