Maternal lead exposure impairs offspring growth and intestinal microbiota via AMPK/ULK1 pathway activation

The pervasive presence and bioaccumulation of lead (Pb^2 +) in living organisms pose a significant risk to human health. Extensive research has been conducted on the neurotoxicity and reproductive toxicity of lead, but the impact of maternal lead exposure on subsequent generations still needs to be addressed. Therefore, we aimed to explore the adverse effects and mechanisms of lead exposure in pregnant mice on the next generation. The present study indicated that lead exposure decreased growth performance and impaired the function of the colon, spleen, testes, and kidneys in the next generation of mice. Furthermore, we found that lead exposure activated autophagy by regulating the AMPK/ULK1 pathway and reduced the relative expression levels of tight junction proteins in a dose-dependent manner. Moreover, the composition of the gut microbiota showed significant alterations compared to the control group. These changes were characterized by a marked reduction in the relative abundance of beneficial bacteria, including Variovorax, Harryflintia, and Romboutsi, while the abundance of pathogenic bacteria such as Mucispirillum and Klebsiella was significantly increased. Such shifts in microbial composition indicated a disruption in microbial homeostasis, contributing to health impairments. In summary, our study indicated that lead exposure in pregnant mice not only decreased the growth performance and impaired multiple organs in the next generation of mice but also disrupted gut microbial homeostasis and induced autophagy via activating the AMPK/ULK1 pathway, resulting in adverse health outcomes in offspring. Additionally, the current study provides a solid experimental foundation for environmental agencies worldwide to implement effective strategies to mitigate lead contamination.