Maternal exposure to tributyltin during early gestation increases adverse pregnancy outcomes by impairing placental development.

Abstract

Tributyltin (TBT) is a persistent organotin pollutant widely used as agricultural and wood biocides, exhibiting well-documented toxicity to reproductive functions in aquatic organisms. However, the effect of TBT on early pregnancy and placental development has been rarely studied in mice. Pregnant mice were fed with 0, 0.2, and 2 mg/kg/day TBT from gravid day 1 to day 8 or 13. TBT exposure led to an increase in the number of resorbed embryo and a reduction in the weight of fetus at gestational days 13. Further study showed that TBT significantly decreased placental weight and area, lowered laminin immunoreactivity and the expressions of placental development-related molecules including Fra1, Eomes, Hand1, and Ascl2. Moreover, TBT treatment markedly inhibited the placental proliferation and induced up-regulation of p53 and cleaved caspase-3 proteins, and down-regulation of Bcl-2 protein. In addition, TBT administration increased levels of malondialdehyde and H2 O2 and decreased activities of catalase and superoxide dismutase. Collectively, these results suggested TBT-induced adverse pregnancy outcomes during early pregnancy might be involved in developmental disorders of the placenta via dysregulation of key molecules, proliferation, apoptosis, and oxidative stress.