Abstract
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.
Highlights
Triclosan (TCS), a broad-spectrum antimicrobial agent, is used in clinical settings and in various personal care and consumer products
By examined seven tissues of pregnant rats exposed to 30–600 mg/kg/day TCS, Feng et al found the greatest bioaccumulation of TCS in the placenta[28]
Our results in the present study indicate that treating pregnant mice with TCS at a dose of 8 mg/kg elicits approximately 24% and 17% decreases in serum total T4 and T3 levels
Summary
Triclosan (TCS), a broad-spectrum antimicrobial agent, is used in clinical settings and in various personal care and consumer products. Animal experiments have shown that the exposure of pregnant mice to TCS causes decreases in fetal body weight and viability[5]. The Akt-mTOR and ERK signaling pathways have been shown to be involved in the placental growth, and placental amino acid transporter function and expression, as well as facilitative GLUT1 membrane localization[20,21,22]. We examined fetal viability and body weight, placental morphological structure and activities and expression of placental System A amino acid or glucose transporters during the exposure to TCS. To explore the underlying mechanisms, we furhter investigated the involvement of TCS-induced hypothyroxinemia in Akt-mTOR-P70S6K and ERK signaling pathways and placental development and function. Our results indicate that TCS-induced hypothyroxinemia impairs placental development and nutrient transfer through down-regulation of Akt-mTOR signaling pathway, leading to decreases in fetal body weight
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