The role of oxygen in prenatal growth: studies in the chick embryo

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.

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Figure 1. Partial pressure of oxygen and haematocrit

Values are means +s.e.m. for chorioallantoic venous blood taken from sea level chick embryos incubated either at sea level (SLSL, open bar, n = 9) or high altitude (SLHA, filled bar, n = 12), high altitude embryos incubated at high altitude (HAHA, stippled bar, n = 10) or sea level (HASL, hatched bar, n = 7), and from sea level chick embryos incubated at high altitude with oxygen supplementation (SLHA + O₂, grey bar, n = 12). Different letters are significantly different by one-way ANOVA with Student–Newman–Keuls test (P < 0.05).

Figure 2. Fetal growth following high and lowland incubations

Values are means +s.e.m. for the egg weight prior to incubation (A), the absolute fetal weight at the end of the incubation period (B) and the fetal weight at the end of the incubation period expressed as a percentage of the initial egg mass (C). SLSL (open bar, n = 31), SLHA (filled bar, n = 19), HAHA (stippled bar, n = 33), HASL (hatched bar, n = 30), and SLHA + O₂ (grey bar, n = 26). Different letters are significantly different by one-way ANOVA with Student–Newman–Keuls or Dunn's tests, as appropriate (P < 0.05).

Figure 3. Symmetry of fetal growth following high and lowland incubations

Values are means +s.e.m. for the body length (A), the head diameter (B), the brain weight expressed as a percentage of the fetal body weight (C) and the ratio of the head diameter to body weight (D). SLSL (open bar, n = 31), SLHA (filled bar, n = 19), HAHA (stippled bar, n = 33), HASL (hatched bar, n = 30), and SLHA + O₂ (grey bar, n = 26). Different letters are significantly different by one-way ANOVA with Dunn's test (P < 0.05).

Figure 4. Use of resource for fetal growth during high and lowland incubations

Values are mean +s.e.m. for the growth efficiency (A) and the partitioning of the resource (B), both expressed as a percentage. SLSL (open bar, n = 31), SLHA (filled bar, n = 19), HAHA (stippled bar, n = 33), HASL (hatched bar, n = 30), and SLHA + O₂ (grey bar, n = 26). Values for partitioning of resource (mean +s.e.m.) are expressed as a histogram on top of the corresponding group. Different letters are significantly different by one-way ANOVA + Student–Newman–Keuls or Dunn's tests, as appropriate (P < 0.05). For calculations with examples, see Methods.