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Early pregnancy failure induced by dibutyltin dichloride in mice
Makoto Ema1, Sakiko Fujii, Tsuguo Ikka
1Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, Tokyo 185-8501, Japan. ema@nihs.go.jp
Abstract:
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.
Insights
Dibutyltin dichloride (DBTCl) exposure during early pregnancy in mice significantly increases embryonic loss and reduces pregnancy success. This adverse effect is linked to decreased progesterone levels, highlighting DBTCl
Area of Science:
- Environmental Toxicology
- Reproductive Toxicology
- Developmental Toxicology
Background:
- Environmental contaminants can disrupt reproductive processes.
- Organotin compounds, like dibutyltin, are known toxicants with potential reproductive effects.
Purpose of the Study:
- To investigate the adverse effects of dibutyltin dichloride (DBTCl) on pregnancy initiation and maintenance.
- To determine the impact of DBTCl administration during early pregnancy in mice.
Main Methods:
- Female ICR mice were administered DBTCl (0, 7.6, 15.2, or 30.4 mg/kg bw/day) via gastric intubation on days 0-3 or 4-7 of pregnancy.
- Pregnancy outcomes were assessed on day 18, including nonpregnant rates, pre- and postimplantation embryonic loss, and fetal malformations.
- Serum progesterone levels were measured.
Main Results:
- DBTCl significantly increased the rate of nonpregnant females and preimplantation embryonic loss at 30.4 mg/kg on days 0-3.
- Postimplantation embryonic loss increased with DBTCl exposure on days 0-3 (≥15.2 mg/kg) and days 4-7 (≥7.6 mg/kg).
- A decline in serum progesterone levels was observed at the highest DBTCl dose (30.4 mg/kg) on both administration periods.
Conclusions:
- DBTCl adversely affects pregnancy initiation and maintenance in mice when administered during early gestation.
- Reduced serum progesterone levels are suggested to be the mechanism underlying DBTCl-induced pregnancy failure.
- DBTCl does not appear to cause external fetal malformations at the tested doses.
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