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Prenatal Stress Differentially Shapes Adult Behavior in Male and Female Offspring

Erbo Dong, Alison Chu, Tamar Gur

    Biorxiv : the Preprint Server for Biology
    |February 27, 2026
    PubMed

    Insights

    Prenatal stress (PNS) impacts male and female offspring differently, increasing anxiety and cognitive issues. This study reveals sex-specific vulnerabilities in social behavior, fear extinction, and alcohol preference following early-life stress.

    Area of Science:

    • Neuroscience
    • Behavioral Science
    • Psychiatry

    Background:

    • Prenatal stress (PNS) is a known risk factor for neuropsychiatric disorders.
    • Sex-specific effects of early-life stress on behavior are not fully understood.
    • Limited studies directly compare male and female offspring responses to stress within the same framework.

    Purpose of the Study:

    • To comprehensively assess sex-dependent behavioral outcomes in adult offspring following prenatal stress.
    • To identify distinct vulnerabilities conferred by prenatal stress in males versus females.
    • To establish a framework for investigating mechanisms of sex-specific stress responses.

    Main Methods:

    • Utilized a validated mouse model of gestational restraint stress.
    • Conducted a within-study, sex-comparative assessment of adult offspring behavior.
    • Evaluated locomotor activity, anxiety, sociability, fear learning/extinction, recognition memory, and alcohol responses using identical paradigms.

    Main Results:

    • Prenatal stress broadly impaired behavior and cognition in both sexes.
    • Sex-specific vulnerabilities included reduced social interaction in males and greater fear extinction impairment and ethanol preference in females.
    • Baseline fear responses, fluid intake, and sucrose consumption remained unaffected.

    Conclusions:

    • Prenatal stress differentially programs neurobehavioral development in a sex-dependent manner.
    • This confers vulnerability to anxiety, cognitive deficits, and alcohol use disorders.
    • The study provides an integrated evaluation of sex-specific PNS outcomes and a framework for mechanistic research.
    Abstract

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