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

Area of Science:

• Developmental toxicology
• Molecular mechanisms of toxicity
• Reproductive toxicology

Background:

• Pentachlorophenol (PCP) is a widely used herbicide and insecticide.
• PCP is suspected to cause carcinogenic, teratogenic, and reproductive effects.
• The molecular mechanisms of PCP's developmental toxicity in mammals are poorly understood.

Purpose of the Study:

• To investigate the developmental toxicity of PCP in mice.
• To elucidate the underlying molecular mechanisms of PCP-induced developmental toxicity, focusing on autophagy.

Main Methods:

• Pregnant ICR mice were exposed to PCP (0.02, 0.2, or 2 mg/kg) from gestation day (GD) 0.5 to GD8.5.
• Fetal loss rates and placental structure (hematoxylin-eosin staining) were assessed on GD16.5.
• Autophagy markers (P62, LC3-II/LC3-I, Beclin1) were analyzed via Western blot and RT-PCR.
• MicroRNA (miR)-30a-5p expression and its interaction with Beclin1 were investigated using bioinformatics, RT-PCR, transfection, and luciferase reporter assays.

Main Results:

• PCP exposure significantly increased fetal loss rates and caused placental chorionic villi structural disorder.
• Autophagosomes were observed in placental tissues, and autophagy markers (P62, LC3-II/LC3-I, Beclin1) were upregulated.
• miR-30a-5p expression was reduced in PCP-treated mice.
• miR-30a-5p directly targets Beclin1, and PCP exposure downregulates miR-30a-5p, leading to Beclin1 upregulation and autophagy.

Conclusions:

• PCP exposure induces developmental toxicity, including fetal loss and placental damage, in mice.
• The mechanism involves PCP downregulating miR-30a-5p, which subsequently upregulates Beclin1, triggering autophagy.
• This study provides novel insights into PCP's developmental toxicity via autophagy-mediated pathways.