Abstract
Background
We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.
Methods
Guinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).
Results
FGR–MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR–MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR–MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR–MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.
Conclusion
Chronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature.
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Acknowledgements
We thank Dr Dan Hardy for his input into this study, Dr Lin Zhao for technical support with the protein analysis, Mr Larry Stitt for statistical support, and Ms Jennifer Ryder for technical assistance with the manuscript.
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Supported by grants from the Children's Health Research Institute and Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada (BSR, TRHR). BSR is the recipient of a Canada Research Chair Tier I in Fetal and Neonatal Health and Development.
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Elias, A., Maki, Y., Matushewski, B. et al. Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with evidence for chronic hypoxia. Pediatr Res 82, 141–147 (2017). https://doi.org/10.1038/pr.2017.92
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DOI: https://doi.org/10.1038/pr.2017.92
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