Constructing an adverse outcome pathway framework for the impact of maternal exposure to PM_2.5 on liver development...

Ambient fine particulate matter (PM_2.5) is a significant contributor to air pollution. PM_2.5 exposure poses a substantial hazard to public health. In recent years, the adverse effects of maternal PM_2.5 exposure on fetal health have gradually gained public attention. As the largest organ in the body, the liver has many metabolic and secretory functions. Liver development, as well as factors that interfere with its growth and function, are of concern. This review utilized the adverse outcome pathway (AOP) framework as the analytical approach to demonstrate the link between maternal PM_2.5 exposure and potential neonatal liver injury from the molecular to the population level. The excessive generation of reactive oxygen species (ROS), subsequent endoplasmic reticulum (ER) stress, and oxidative stress were regarded as the essential components in this framework, as they could trigger adverse developmental outcomes in the offspring through DNA damage, autophagy dysfunction, mitochondrial injury, and other pathways. To the best of our knowledge, this is the first article based on an AOP framework that elaborates on the influence of maternal exposure to PM_2.5 on liver injury occurrence and adverse effects on liver development in offspring. Therefore, this review offered mechanistic insights into the developmental toxicity of PM_2.5 in the liver, which provided a valuable basis for future studies and prevention strategies.