Maternal depression and offspring neurodevelopmental impairments in wild rodents induced by ecologically relevant prenatal stress

Mol Psychiatry. 2025 Sep 13. doi: 10.1038/s41380-025-03258-9. Online ahead of print.

ABSTRACT

Prenatal maternal stress negatively impacts maternal mental health and mother-child interaction, potentially increasing the risk of developmental outcomes in offspring. While studies in humans and lab animals have established these associations, the underlying mechanisms in naturalistic settings, where stressors are dynamic and interspecies differences may emerge, remain poorly characterized. This study introduced a novel model system using wild Brandt’s voles (Lasiopodomys brandtii) to investigate the effects of maternal depression-like psychopathology on offspring mood, cognition, and brain development. This model involves the repeated exposure of pregnant voles to predator odors, a natural stressor, which induces a depression-like state from late pregnancy to the early postpartum period. This model integrates ecologically relevant stressors with neurobehavioral assessments in a wild-derived species, allowing for a mechanistic investigation in a biologically meaningful context. We found that while exposure to predator odor stress during pregnancy induced maternal depressive-like states, it did not alter the level of postnatal parent-offspring interaction. Offspring born to mothers exposed to predator odor during pregnancy exhibited increased anxiety- and depression-like behaviors, impaired spatial and social cognition, and reduced sociability compared to offspring of mothers exposed to distilled water. These offspring also showed reduced neurogenesis in the hippocampal dentate gyrus, along with decreased dendrite branching and spine density. Our findings suggest that the effects of depression-like states during pregnancy and postpartum in female Brandt’s voles on offspring brain and behavioral functions occur independently of parent-offspring interactions, with hippocampal structural and functional abnormalities potentially mediating behavioral deficits. Importantly, this work establishes Brandt’s voles as a new, ecologically valid animal model for studying gestational depression and its intergenerational outcomes, bridging the gap between laboratory rodent studies and natural behavioral contexts.

PMID:40946096 | DOI:10.1038/s41380-025-03258-9