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Updated: Aug 5, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal
Shirelle X Liu1, Tenille K Fredrickson1, Natalia Calixto Mancipe2
1Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Insights
Early iron deficiency (ID) in rats causes sex-specific brain changes. Prenatal choline partially reversed these effects, particularly in females, revealing crucial molecular pathways for neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Genomics
Background:
- Fetal-neonatal iron deficiency (ID) leads to lasting neurocognitive and affective issues.
- Early-life ID exhibits sex-specific effects on brain development.
- Molecular mechanisms of sex-specific neural gene regulation in early ID are poorly understood.
Purpose of the Study:
- To investigate sex-specific transcriptome alterations in adult rat hippocampus.
- To examine the impact of fetal-neonatal ID and prenatal choline treatment on gene expression.
Main Methods:
- Pregnant rats received iron-deficient or iron-sufficient diets with/without choline supplementation.
- Hippocampi from adult offspring (P65) of both sexes were analyzed for gene expression changes.
Main Results:
- Early ID and choline induced significant transcriptional changes in both sexes.
- ID enhanced neuroinflammation networks; females showed altered oxidative phosphorylation and fatty acid metabolism compared to males.
- Prenatal choline partially rescued ID-induced dysregulation, especially in females, and altered gene expression in iron-sufficient rats.
Conclusions:
- Early iron and choline impact hippocampal gene expression in a sex-specific manner, with greater effects in females.
- Findings highlight potential sex-specific gene networks regulated by iron and choline for future research.
Background:
Fetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies have shown that early-life ID produces sex-specific effects. However, little is known about the molecular mechanisms underlying these early-life ID-induced sex-specific effects on neural gene regulation.
Objective:
To illustrate sex-specific transcriptome alterations in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment.
Methods:
Pregnant rats were fed an iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11-18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression.
Results:
Both early-life ID and choline treatment induced transcriptional changes in adult female and male rat hippocampi. Both sexes showed ID-induced alterations in gene networks leading to enhanced neuroinflammation. In females, ID-induced changes indicated enhanced activity of oxidative phosphorylation and fatty acid metabolism, which were contrary to the ID effects in males. Prenatal choline supplementation induced the most robust changes in gene expression, particularly in iron-deficient animals where it partially rescued ID-induced dysregulation. Choline supplementation also altered hippocampal transcriptome in iron-sufficient rats with indications for both beneficial and adverse effects.
Conclusions:
This study provided unbiased global assessments of gene expression regulated by iron and choline in a sex-specific manner, with greater effects in female than male rats. Our new findings highlight potential sex-specific gene networks regulated by iron and choline for further investigation.
