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Updated: Apr 30, 2026
Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Elevated maternal testosterone induces sex-specific neurodevelopmental changes and ASD-related behavioral phenotypes
Jay S Mishra1, Sai Krishna Bhamidipati1, Jordan Ronald Ross1
1Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Objective:
Elevated maternal testosterone (T) during pregnancy disrupts neurodevelopment and behavior in offspring, mimicking features of autism spectrum disorder (ASD).
Methods:
In a rat study, dams received daily T injections (0.5 mg/kg) from gestational days 12-20, doubling maternal plasma T to mimic levels seen in pregnancy complications. Controls received vehicle. Offspring were assessed neonatally (postnatal day 9) for communication (ultrasonic vocalizations), neurogenesis (NeuN+ neurons), myelination (MBP+ area), and brain docosahexaenoic acid (DHA). Adolescent offspring (6-8 weeks) underwent behavioral tests for cognition (Y-maze, novel object recognition) and sociability (three-chamber test).
Results:
T-exposed pups had lower birth weights and reduced vocalizations during maternal separation. Sex-specific neural changes observed: males showed reduced cortical neuron density, while females had diminished corpus callosum myelination. Both sexes exhibited decreased brain DHA. In adolescence, T offspring displayed cognitive deficits (impaired spatial/recognition memory) and social impairments (reduced sociability and social novelty preference).
Conclusion:
The study highlights maternal T as a risk factor for neurodevelopmental disorders, with sex-specific effects on brain structure and function. Reduced brain DHA suggests a mechanistic link, implicating lipid metabolism in T-associated neurodevelopmental disruptions. These findings support further exploration of DHA supplementation as a therapeutic strategy to mitigate adverse outcomes in high-risk pregnancies.
Impact:
Elevated maternal testosterone (T) during pregnancy induces ASD-like neurobehavioral deficits (e.g., impaired communication, social/cognitive dysfunction) and sex-specific neural alterations in offspring. Prenatal T differentially impacts male vs. female brain structure: T-exposed males show cortical neuron loss, while females exhibit myelination deficits in the corpus callosum. First to connect maternal T-driven offspring brain docosahexaenoic acid (DHA) reduction to neurodevelopmental impairment. Supports prenatal DHA supplementation as a strategy to mitigate neurodevelopmental risks in high-T pregnancies. Informs policies addressing rising neurodevelopmental disorder rates linked to maternal metabolic/endocrine imbalances.
