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.
Highlights
Spontaneous abortion is the most common complication of human pregnancy and 10–15% of clinical pregnancies end in it[1]
According to the level of urinary TCS in spontaneous abortion patients, we prepared the model of pregnant mouse exposed to TCS, in which the fetal survival and development were examined during mid- to late gestation
Our results indicated that the exposure of TCS in humans and mice might cause spontaneous abortion in mid-gestation probably through the inhibition of estrogen sulfotransferase (EST) activity leading to placental thrombosis and degeneration
Summary
Spontaneous abortion is the most common complication of human pregnancy and 10–15% of clinical pregnancies end in it[1]. Triclosan (TCS), an antibacterial agent, is widely used in soaps, toothpastes, first-aid products, fabrics and plastic goods[3,4] This compound has been identified in the mother’s milk, the plasma of people in Sweden and Australia[5,6] and the urine of people in the United States[7]. According to the level of urinary TCS in spontaneous abortion patients, we prepared the model of pregnant mouse exposed to TCS, in which the fetal survival and development were examined during mid- to late gestation. Placental structure, the levels of reproductive hormones and thyroid hormones, the expression and activity of EST were further examined in spontaneous abortion patients and TCS-exposed pregnant mice. Our results indicated that the exposure of TCS in humans and mice might cause spontaneous abortion in mid-gestation probably through the inhibition of EST activity leading to placental thrombosis and degeneration
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