Placental Igf1 Overexpression Sex-Specifically Impacts Mouse Placenta Structure, Altering Offspring Striatal Development and Behavior

Annemarie J. Carver; Faith M. Fairbairn; Robert J. Taylor; Shanmukh Boggarapu; Njenga R. Kamau; Amrita Gajmer; Hanna E. Stevens

doi:10.1101/2025.03.27.644829

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Placental Igf1 Overexpression Sex-Specifically Impacts Mouse Placenta Structure, Altering Offspring Striatal Development and Behavior

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Placental Igf1 Overexpression Sex-Specifically Impacts Mouse Placenta Structure, Altering Offspring Striatal Development and Behavior

Annemarie J. Carver, Faith M. Fairbairn, Robert J. Taylor, Shanmukh Boggarapu, Njenga R. Kamau, Amrita Gajmer and Hanna E. Stevens

bioRxiv

Cold Spring Harbor Laboratory, 1.1

03/28/2025

DOI: 10.1101/2025.03.27.644829

PMCID: PMC11974794

PMID: 40196637

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https://doi.org/10.1101/2025.03.27.644829View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Insulin-like growth factor 1 (IGF1) is produced primarily in the placenta in utero and is an essential hormone for neurodevelopment. Specifically, how placental IGF1 production persistently influences the brain is unclear. This study evaluated the effects of placental Igf1 overexpression on embryonic and postnatal brain development, particularly for striatum, a region highly linked to neurodevelopmental disorders. Placental Igf1 was overexpressed via placental-targeted CRISPR manipulation. This overexpression altered placenta structure and function distinctly in females and males. Early differences in placental function altered the trajectory of striatal development, as adult females showed persistent changes in striatal cell composition and striatal dependent behavior while males were less affected in brain and behavior outcomes. Overall, these results demonstrate that placental Igf1 expression alters striatal development and behavior in ways relevant to neurodevelopmental disorders. These findings expand our understanding of placental influence on neurodevelopment and will aid in identifying placental-targeted preventive interventions.

Developmental Biology

Details

Title: Subtitle: Placental Igf1 Overexpression Sex-Specifically Impacts Mouse Placenta Structure, Altering Offspring Striatal Development and Behavior
Creators: Annemarie J. Carver - University of Iowa
Faith M. Fairbairn - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa
Robert J. Taylor - University of Iowa
Shanmukh Boggarapu - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa
Njenga R. Kamau - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa
Amrita Gajmer - Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa
Hanna E. Stevens - Hawk-Intellectual and Developmental Disabilities Research Center, University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.03.27.644829
PMID: 40196637
PMCID: PMC11974794
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 48
Language: English
Date posted: 03/28/2025
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984808538902771

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