Maternal pentachlorophenol exposure induces developmental toxicity mediated by autophagy on pregnancy mice

Pentachlorophenol (PCP) is often used as chlorinated hydrocarbon herbicides and insecticides, which has been suggested that toxicity of carcinogenic effect, teratogenic effect and reproductive system. However, there was still precious known about the underlying molecular mechanism of PCP on mammalian early development. To explore the developmental toxicity of PCP and its potential mechanism, pregnancy ICR mice except controls were exposed to PCP (0.02, 0.2 or 2 mg/kg) during gestation day (GD) 0.5 to GD8.5 in this study. We found that the fetal loss rate was increased and placental chorionic villi structure was disorder in hematoxylin-eosin staining (HE) on GD16.5. Meanwhile, autophagosomes were observed in chorionic villi through Transmission Electron Microscope (TEM). Moreover, the mRNA and/or protein expression of P62, LC3-II/LC3-I and Beclinl were increased in placenta, indicating the occurrence of autophagy. Then, to further explore the autophagy mechanism, microRNA (miR)-30a-5p, an expression inhibitor of Beclinl, was predicted through bioinformatics predictions and RT-PCR, and it was reduced in PCP-treated mice. Transfection and luciferase reporter gene test were used to verify the interaction between Beclinl and miR-30a-5p. These results firstly indicate that, PCP exposure could downregulate the expression of miR-30a-5p, and then induced autophagy through upregulation of Beclinl to result in fetal loss. Our study laid a foundation for understanding the PCP developmental toxicity through autophagy.