title: Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice.
abstract: Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5-16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis.
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chang
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced* / Q000201:enzymology* / Q000652:urine; D000818:Animals; D015415:Biomarkers; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D042341:Gonadal Hormones / Q000097:blood; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology; D006801:Humans; D051379:Mice; D016017:Odds Ratio; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D015238:Sulfotransferases / Q000378:metabolism* / Q000652:urine; D013927:Thrombosis / Q000209:etiology / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D014260:Triclosan / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D042341:Gonadal Hormones; D013963:Thyroid Hormones; D014260:Triclosan; D015238:Sulfotransferases; C020122:estrone sulfotransferase