Exposure of pregnant mice to triclosan impairs placental development and nutrient transport.
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.
State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.
Xinyuan
X
Cao
Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.
Xu
X
Hua
Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.|Department of Pharmacology, Nanjing Medical University, Nanjing, 211166, China.
Xiaoli
X
Wang
State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.|Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.
Ling
L
Chen
D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D049109:Cell Proliferation; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D006728:Hormones / Q000097:blood; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009929:Organ Size; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010929:Placentation / Q000187:drug effects*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014260:Triclosan / Q000009:adverse effects*
D026905:Amino Acid Transport Systems; D051246:Glucose Transport Proteins, Facilitative; D006728:Hormones; D014260:Triclosan; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases