Basic Science Article | Published:

Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with increased brain apoptosis

Pediatric Research (2018) | Download Citation

Subjects

Abstract

Background

We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts cell death in the brain with implications for neurodevelopmental adversity.

Methods

Guinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Fetuses were necropsied near term and brain tissues processed for necrosis (H&E), apoptosis (TUNEL), and pro- (Bax) and anti- (Bcl-2 and Grp78) apoptotic protein immunoreactivity.

Results

FGR-MNR fetal and brain weights were decreased 38% and 12%, respectively, indicating brain sparing but with brains still smaller. While necrosis remained unchanged, apoptosis was increased in the white matter and hippocampus in the FGR brains, and control and FGR-related apoptosis were increased in males for most brain areas. Bax was increased in the CA4 and Bcl-2 was decreased in the dentate gyrus in the FGR brains supporting a role in the increased apoptosis, while Grp78 was increased in the FGR females, possibly contributing to the sex-related differences.

Conclusions

MNR-induced FGR results in increased brain apoptosis with regional and sex-related differences that may contribute to the reduction in brain area size reported clinically and increased risk in FGR males for later neurodevelopmental adversity.

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Acknowledgements

We thank Dr Lin Zhao for support with the protein analysis, and Ms Jennifer Ryder for assistance with the manuscript. Supported by grants from the Children’s Health Research Institute and Department of Obstetrics and Gynecology, The University of Western Ontario, London, Canada (B.S.R., R.H.)

Author information

Affiliations

  1. Departments of Obstetrics and Gynecology, Physiology and Pharmacology, Pediatrics, and Pathology, Children’s Health Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada

    • Andrew Ghaly
    • , Yohei Maki
    • , Karen Nygard
    • , Robert Hammond
    • , Daniel B. Hardy
    •  & Bryan S. Richardson

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Contributions

The authors contributed to all three aspects of the Pediatric Research criteria.

Competing interests

B.S.R. is the recipient of a Canada Research Chair Tier 1 in Fetal and Neonatal Health and Development. All the remaining authors declare no competing interests.

Corresponding author

Correspondence to Bryan S. Richardson.

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DOI

https://doi.org/10.1038/s41390-018-0230-6