Prenatal triclosan exposure impairs mammalian lung branching morphogenesis through activating Bmp4 signaling

产前三氯生暴露通过激活 Bmp4 信号传导损害哺乳动物肺分支形态发生

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作者:Qiuling Li, Yulong Qiao, Feifei Wang, Jian Zhao, Lijun Wu, Honghua Ge, Shengmin Xu

Abstract

Triclosan (TCS) is a commonly used antibacterial agent present in personal care and household products. Recently, there have been increasing concerns about the association between children's health and TCS exposure during gestation, but the toxicological effects of TCS exposure on embryonic lung development remain undetermined. In this study, through using an ex vivo lung explant culture system, we found that prenatal exposure to TCS resulted in impaired lung branching morphogenesis and altered proximal-distal airway patterning. These TCS-induced dysplasias are accompanied by significantly reduced proliferation and increased apoptosis within the developing lung, as a consequence of activated Bmp4 signaling. Inhibition of Bmp4 signaling by Noggin partially rescues the lung branching morphogenesis and cellular defects in TCS-exposed lung explants. In addition, we provided in vivo evidence that administration of TCS during gestation leads to compromised branching formation and enlarged airspace in the lung of offspring. Thus, this study provides novel toxicological information on TCS and indicated a strong/possible association between TCS exposure during pregnancy and lung dysplasia in offspring.

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