Prenatal acetaminophen exposure induces changes of placental morphology and function and its influencing factors.

Acetaminophen is a commonly used antipyretic and analgesic during pregnancy. The placenta plays a crucial role in fetal development. In this study, we investigated the impact of different doses (100 or 400 mg/kg·d), courses (gestational day 12 or 10-12), and stages (gestational day 12 or 15-17) on placental development in mice. The results indicated that prenatal acetaminophen exposure (PAcE) leads to necrosis of trophoblast cells and disruption of septa. Additionally, the expression of placental cell proliferation genes was reduced, while the expression of apoptosis genes was elevated. Expression of glucose transporter genes (Glut1, Glut3), amino acid transporter gene (Lat2), and cholesterol uptake genes (Ldlr, Srb1) was increased, whereas the expression of cholesterol transport genes (Abca1, Abcg1) and fatty acid transporter genes (Cd36, Fatp1) was significantly reduced. These changes were more pronounced in the high-dose, single-course, third-trimester, and female placentas. Further analysis revealed that PAcE significantly suppressed the expression of the IGF1/2 signalling pathway. Correlation analysis suggested a strong association between IGF1/2 signalling pathway and placental genes. In summary, this study confirmed that PAcE induced changes in morphological and functional development. Dose, course, stage, and sex are important influencing factors. This study would provide a reference for the developmental toxicity of acetaminophen during pregnancy.