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The role of oxygen in prenatal growth: studies in the chick embryo
Dino A Giussani1, Carlos E Salinas, Mercedes Villena
1Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK. dag26@cam.ac.uk
Insights
Fetal oxygen levels significantly impact prenatal growth, independent of maternal nutrition. Studies in chickens show high altitude restricts growth, but prolonged exposure offers protection against low oxygen effects.
Area of Science:
- Developmental Biology
- Physiology
- Altitude Research
Background:
- Small birth size is linked to cardiovascular disease, increasing interest in fetal growth determinants.
- Genes and nutrition are known factors, but the role of fetal oxygenation was previously unisolated.
- The chicken model allows direct assessment of oxygenation effects on fetal growth without maternal variables.
Purpose of the Study:
- To investigate the predominant role of oxygen in regulating prenatal growth.
- To isolate the effects of altered fetal oxygenation on fetal development.
- To determine if prolonged high-altitude exposure impacts fetal growth regulation.
Main Methods:
- Fertilized chicken eggs from sea-level and high-altitude hens were incubated under varying oxygen conditions (sea level and high altitude).
- Fetal growth was assessed under different oxygenation levels, controlling for maternal physiology and nutrition.
- Oxygen supplementation was used to counteract high-altitude effects.
Main Results:
- High-altitude incubation restricted fetal growth in eggs from sea-level hens.
- Eggs from high-altitude hens showed less growth restriction at high altitude and enhanced growth at sea level.
- Oxygen supplementation prevented growth restriction caused by high-altitude incubation.
Conclusions:
- Fetal oxygenation is a primary regulator of prenatal growth, independent of maternal nutrition.
- Prolonged high-altitude residence provides a protective effect against hypoxia-induced fetal growth restriction.
- The study highlights oxygen's critical role in fetal development and adaptation to environmental conditions.
Abstract:
The compelling evidence linking small size at birth with later cardiovascular disease has renewed and amplified scientific and clinical interests into the determinants of fetal growth. It is accepted that genes and nutrition control fetal growth; however, prior to this study, it had been impossible to isolate the effect of increases and decreases in fetal oxygenation on the regulation of prenatal growth. We investigated the role of oxygen in the control of fetal growth in the chicken because in contrast to mammals, the effects on the fetus of changes in oxygenation could be isolated, by assessing them directly without alteration to the maternal or placental physiology or maternal nutrition during development. The data show that incubation at high altitude of fertilized eggs laid by sea level hens markedly restricted fetal growth. Incubation at high altitude of fertilized eggs laid by high altitude hens also restricted fetal growth, but to a lesser extent compared to eggs laid by sea level hens. By contrast, incubation at sea level of fertilized eggs laid by high altitude hens not only restored, but enhanced, fetal growth relative to sea level controls. Incubation at high altitude of sea level eggs with oxygen supplementation completely prevented the high altitude-induced fetal growth restriction. Thus, fetal oxygenation, independent of maternal nutrition during development, has a predominant role in the control of fetal growth. Further, prolonged high altitude residence confers protection against the deleterious effects of hypoxia on fetal growth.

