Prenatal Stress Differentially Shapes Adult Behavior in Male and Female Offspring

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.