Exposure of pregnant mice to triclosan impairs placental development and nutrient transport.
Exposure of pregnant mice to triclosan impairs placental development and nutrient transport.
复制标题
怀孕小鼠接触三氯生会损害胎盘发育和营养物质运输。
DOI：
10.1038/srep44803
复制
发表时间：
2017-03-21
影响因子：
4.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Cao X;Hua X;Wang X;Chen L
三氯生(TCS)与自然流产和胎儿生长受限有关。在这里，我们发现当妊娠小鼠在妊娠天数(GD)内给予8 mg/kg天花粉蛋白时，6-18胎体重低于对照组。8-TCS小鼠胎盘重量和体积减少。8-TCS小鼠GD13胎盘增殖细胞、增殖细胞核抗原和细胞周期蛋白D3表达明显减少。8-TCS小鼠GD14和GD17胎盘系统A氨基酸或葡萄糖转运蛋白的活性和表达均降低。8-TCS组小鼠血清甲状腺激素(T4)和三碘甲腺原氨酸(T3)水平低于对照组。L-甲状腺素(T4)可纠正8-TCS小鼠胎盘AKT、mTOR和p70S6K磷酸化水平的下降。8-TCS小鼠经T4处理后，胎盘细胞的增殖受到抑制，对mTOR敏感的氨基酸和葡萄糖转运蛋白的活性和表达有所恢复。此外，T4的替代可以挽救雷帕霉素所阻断的胎儿体重的下降。这些结果表明，TCS通过减少Akt-mTOR信号通路诱导妊娠小鼠低甲状腺素血症可能损害胎盘发育和营养物质的转运，导致胎儿体重下降。
Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6–18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight.