Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome

Shirelle X. Liu, Tenille K. Fredrickson, Natalia Calixto Mancipe, Michael K. Georgieff, Phu V. Tran

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1316
JournalNutrients
Volume15
Issue number6
DOIs
StatePublished - Mar 2023

Bibliographical note

Funding Information:
This work was funded by NIH R01NS099178 to P.V.T. and R01HD29421 to M.K.G.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • choline
  • hippocampus
  • iron deficiency
  • sex difference
  • transcriptome

PubMed: MeSH publication types

  • Journal Article

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