Comparative Analysis of Prenatal Stress Models: Placental and Neurodevelopmental Outcomes in Mice

Mia Dukle; Faith M Fairbairn; Sara V Maurer; Madelyn M Grueter; Ahmed I Baig; Rachel Telles; Hanna E Stevens

doi:10.59249/MHFP3728

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Comparative Analysis of Prenatal Stress Models: Placental and Neurodevelopmental Outcomes in Mice

Journal article

Open access

Peer reviewed

Comparative Analysis of Prenatal Stress Models: Placental and Neurodevelopmental Outcomes in Mice

Mia Dukle, Faith M Fairbairn, Sara V Maurer, Madelyn M Grueter, Ahmed I Baig, Rachel Telles and Hanna E Stevens

The Yale journal of biology & medicine, Vol.99(1), pp.127-141

03/2026

DOI: 10.59249/MHFP3728

PMCID: PMC13023424

PMID: 41918509

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Abstract

Prenatal stress affects offspring development. The placenta, an important maternal-fetal mediator, is susceptible to prenatal stress, and its biology affects fetal neurodevelopment, particularly ventral forebrain. Ventral forebrain developmental disruption is linked to neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Currently, multiple mouse models are used to study these links. However, each model may induce unique effects in both placental and neurodevelopmental outcomes, which are rarely studied. To explore this, pregnant mice were exposed 3 times daily to one of three stress models: repeated restraint stress (RS), chronic unpredictable stress (CUS), or repeated footshock stress (FS) beginning at embryonic day (E)12. At E14 or E18, placenta and embryonic brain were collected, and qPCR and brain stereological measurements were performed. Placental immune and ventral forebrain GABAergic gene expression was impacted more at E14, with many changes not apparent by E18, suggesting an acute dysregulated state. Different models had both unique and overlapping effects. E18 analyses suggested adaptation to stress over time, with overall suppression or lack of placental immune factor changes, fewer deviations in the brain, and correlations between placenta and brain, particularly in females. Chronic unpredictable stress showed the most changes at E18. These findings suggest that, while each model has unique effects, as stress exposure progresses, placental immune functioning may promote the normalization of brain GABAergic systems, particularly in females. Further understanding the placenta-brain axis may be valuable in delineating mechanisms that increase and decrease risk of neurodevelopmental disorders.

Pregnancy

Animals

Brain - embryology

Disease Models, Animal

Female

Male

Mice

Mice, Inbred C57BL

Neurodevelopmental Disorders

Placenta - metabolism

Prenatal Exposure Delayed Effects

Stress, Psychological

Details

Title: Subtitle: Comparative Analysis of Prenatal Stress Models: Placental and Neurodevelopmental Outcomes in Mice
Creators: Mia Dukle - University of Iowa
Faith M Fairbairn - University of Iowa
Sara V Maurer - University of Iowa
Madelyn M Grueter - University of Iowa
Ahmed I Baig - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, IA, USA
Rachel Telles - University of Iowa
Hanna E Stevens - University of Iowa
Resource Type: Journal article
Publication Details: The Yale journal of biology & medicine, Vol.99(1), pp.127-141
DOI: 10.59249/MHFP3728
PMID: 41918509
PMCID: PMC13023424
NLM abbreviation: Yale J Biol Med
ISSN: 1551-4056
eISSN: 1551-4056
Language: English
Date published: 03/2026
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9985149086802771

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