Effects of perinatal exposure to low doses of tributyltin chloride on pregnancy outcome and postnatal development in mouse offspring.

Tributyltin (TBT), an endocrine-disrupting chemical, is well known to induce imposex in female gastropods. In this study, we assessed the effects of low doses of tributyltin chloride (TBTCl) on dams and their offspring. Pregnant mice were administered by gavage with 0, 1, 10, or 100 µg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. There were no TBT treatment-related deaths or clinical signs of toxicity for dams, and no treatment-related effects on body weight, litter sizes, gestational length of dams, and sex ratio, lactational body weight, postnatal survival, age at eruption of incisors, and eye opening of pups. However, at 100 µg/kg, TBTCl retarded the testes descent of male offspring. Behavioral tests showed a significant delay in cliff-drop aversion response in offspring of 10 and 100 µg/kg groups, but no significant difference in the righting reflex between control and TBT-exposed offspring was detectable. These results indicate that neurobehavioral toxicity seems to be one sensitive indicator to assess the risk of low doses of TBT.

Perinatal exposure to low doses of tributyltin chloride advances puberty and affects patterns of estrous cyclicity in female mice.

Tributyltin (TBT), a proven endocrine-disrupting chemical, is well known to induce imposex in female gastropods. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on the female offspring of KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 µg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically advanced the age of onset of vaginal opening (VO) and first vaginal estrus, and reduced body weights at VO and first estrus. Furthermore, perinatal treatment with TBTCl significantly reduced the number of days between VO and first estrus. In addition, female offspring from dams exposed to 10 and 100 µg kg(-1) TBTCl exhibited altered patterns of estrous cyclicity in adulthood. In conclusion, perinatal exposure to low doses TBTCl result in early puberty and impaired estrous cyclicity in female mice, which suggest that TBTCl might act as an estrogen agonist or/and a disruptor on hypothalamic-pituitary function in the present study.