Department of Physiology, Basic Medical College, Nanchang University, Nanchang, China.
Department of Clinic Medicine, School of Queen Mary, Nanchang University, Nanchang, China.
Environ Toxicol. 2021 Jul;36(7):1303-1315. doi: 10.1002/tox.23127. Epub 2021 Mar 15.
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 H O 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.
三丁基锡（TBT）是一种持久性有机锡污染物，广泛用作农业和木材杀生剂，对水生生物的生殖功能具有良好的毒性记录。然而，TBT 对小鼠早期妊娠和胎盘发育的影响很少被研究。从妊娠第 1 天到第 8 天或第 13 天，怀孕的老鼠每天喂食 0、0.2 和 2 毫克/千克的 TBT。TBT 暴露导致胚胎吸收率增加，妊娠第 13 天胎儿体重降低。进一步的研究表明，TBT 显著降低了胎盘重量和面积，降低了层粘连蛋白的免疫反应性以及胎盘发育相关分子 Fra1、Eomes、Hand1 和 Ascl2 的表达。此外，TBT 处理明显抑制了胎盘的增殖，并诱导了 p53 和 cleaved caspase-3 蛋白的上调，以及 Bcl-2 蛋白的下调。此外，TBT 给药增加了丙二醛和 H2O2 的水平，降低了过氧化氢酶和超氧化物歧化酶的活性。总之，这些结果表明，TBT 诱导的早期妊娠不良妊娠结局可能通过调节关键分子、增殖、凋亡和氧化应激来参与胎盘发育障碍。
