Impact of prenatal environmental exposure on offspring neurodevelopment and susceptibility to neurodegenerative diseases: mechanisms and perspectives

Abstract

Pregnancy constitutes a critical window for fetal nervous system development. Maternal environmental exposure can trigger placenta-mediated intrauterine perturbations, exerting persistent programming effects on fetal neural development and elevating the susceptibility to neurodegenerative diseases in adulthood. This review systematically summarizes typical prenatal exposure types, including air pollutants, heavy metals, endocrine-disrupting chemicals, nutritional imbalance, and maternal stress. Focusing on four core mechanistic pathways—epigenetic modification, oxidative stress, neuroinflammation, and mitochondrial dysfunction—this study integrates epidemiological evidence, animal model data, and molecular mechanistic findings to elaborate how early-life environmental exposure reshapes neurodevelopmental trajectories and mediates long-term neurological damage. Notably, this review highlights the interactive feedback and cascade amplification effects among multiple biological mechanisms, and strictly distinguishes well-established causal associations from speculative inferences. This work constructs a stratified evidence framework for the developmental origin theory of neurodegenerative diseases, providing scientific support for precise pre-pregnancy and prenatal disease prevention and intervention strategies.