Parental Exposures and Offspring Brain Outcomes: Epigenetic and Molecular Mechanisms

What parents experience before conception and during pregnancy can leave a lasting impact on offspring brain development. Maternal factors, including stress, diet, infection, and exposure to drugs or environmental chemicals, have all been linked to alterations in neurodevelopment and behavior. Less obvious, but now well documented, is that paternal experience matters too: a father’s diet, age, and stress can alter the sperm epigenome and influence the next generation. Consequently, the central question driving this field is no longer whether these effects exist, but how they are encoded, passed on, and turned into changes in neural circuits.

Most of the answers point to epigenetics. Mechanisms such as DNA methylation, histone modifications, and small non-coding RNAs carried in the germline can adjust gene expression in the developing brain without altering the underlying sequence. These epigenetic marks shape key processes, including neurogenesis, synapse formation, dendritic growth, and circuit wiring, during sensitive developmental windows, often persisting long after the original exposure. On the maternal side, the placenta acts as a critical interface, relaying nutritional and inflammatory signals to the fetal brain. Conversely, on the paternal side, the reprogramming of the sperm epigenome provides a pathway for environmental experience to influence offspring, even in the absence of a shared gestational environment.
We still understand the associations far better than the underlying mechanisms. Fundamental questions remain: how does a given exposure select particular molecular pathways? Why do some effects fade while others are inherited across generations? And how do these early life changes set the stage for later plasticity and disease susceptibility? Distinguishing causality from correlation, and mapping the molecular steps that bridge the two is the primary objective of this collection.

This Research Topic welcomes submissions exploring the epigenetic and molecular mechanisms linking parental exposures to offspring brain development and plasticity. We encourage research examining parental contributions, particularly studies that trace the trajectory from initial exposure to molecular changes and subsequent circuit and behavioral outcomes. We invite research that addresses, but are not limited to, the following themes:

o Epigenetic and post-transcriptional regulation of offspring neurodevelopment following parental exposure, through DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (miRNAs, lncRNAs, circRNAs).
o Maternal environmental factors (stress, diet, infection, or exposure to drugs and chemicals) and their molecular impact on neural development and plasticity.
o Molecular mechanisms through which maternal nutrition and metabolic state shape the brain epigenome, regulating neurogenesis, synaptogenesis, dendritic remodeling, and synaptic plasticity.
o Impact of maternal metabolic disorders (e.g., obesity, diabetes, hyperhomocysteinemia) on offspring brain epigenetics and neurodevelopment.
o Gene-diet interactions, nutrigenomics, and dietary bioactive compounds (e.g., one-carbon metabolites, phytochemicals) in the epigenetic regulation of neural circuit formation and behavior.
o Paternal exposures and germline transmission via the sperm epigenome.
o Mechanisms of intergenerational and transgenerational epigenetic inheritance of brain-related phenotypes, with rigorous generational design.
o The placenta as a molecular interface mediating maternal-fetal signaling and offspring brain programming.
o Sex-specific differences in epigenetic programming and neurodevelopmental outcomes.
o Critical developmental windows of epigenetic vulnerability and plasticity during prenatal and early postnatal life.
o Disruption of developmental plasticity and its links to neurodevelopmental disorders, including the reversibility of epigenetic changes through dietary, pharmacological, or lifestyle interventions.
o Epigenetic mechanisms linking parental exposures to cognition, learning, memory, and emotional behavior, with molecular and behavioral readouts in animal, organoid, and iPSC-based models.

Article types welcomed: Original Research, Review, Mini Review, Methods, Brief Research Report, Perspective, and more

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Maternal nutrition, Epigenetic regulation, Neurodevelopmental programming, Neuroplasticity, DNA methylation, Brain development

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.