Epigenetic Mechanisms Linking Maternal Stress During Pregnancy to Autism Spectrum Disorders: A Narrative Review

Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and the presence of restricted, repetitive behaviors. While genetic factors contribute substantially to ASD etiology, growing evidence highlights the role of environmental and epigenetic factors, with maternal stress during pregnancy emerging as a potential determinant of fetal brain development. Prenatal stress may alter the intrauterine environment through modulation of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid signaling. These physiological responses have been associated with epigenetic modifications, such as DNA methylation, histone post-translational modifications, and alterations in non-coding RNA expression although causal pathways remain under investigation. Consequently, gene expression programs critical for neuronal proliferation, migration, synaptogenesis, and stress-response maturation are reshaped. Converging evidence from human cohorts and animal models indicates that these stress-induced epigenetic changes affect genes such as NR3C1, FKBP5, BDNF, OXTR, and SHANK3, contributing to altered stress response, impaired synaptic plasticity, and disrupted neural connectivity. Foundational studies before 2020 established the basic mechanistic link between prenatal stress, glucocorticoid exposure, and epigenetic gene regulation, forming a basis for the 2020-2025 literature summarized here. This narrative review synthesizes research published between 2020 and 2025, integrating molecular, epidemiological, and neurodevelopmental perspectives to elucidate how prenatal stress induces lasting neurobiological changes, thereby advancing the conceptual framework for early detection and intervention in ASD.