Prenatal development of the pulmonary surfactant system and the influence of hypoxia

Pulmonary surfactant fulfils diverse functions at the lung air–liquid interface of all air-breathing vertebrates. Neurohormonal regulation of surfactant synthesis and secretion is highly conserved among non-mammalian amniotes. Although the pattern of surfactant lipid maturation is similar among species, the onset and completion differ dramatically. These differences are apparently not determined by phylogeny, but may relate to the timing of development of relative hypoxia as an embryo develops, which is related to birthing strategy. We have proposed that hypoxia is an evolutionary drive for differential surfactant development among species. In mammalian and non-mammalian models, hypoxia induces fetal growth restriction. Depending on the timing of the insult, this may be associated with an acceleration or deceleration of surfactant development. The hypoxic effect may be mediated via hormonal and growth factors, such as glucocorticoids and VEGF. However, the multifactorial nature of mammalian growth restriction models complicates the mechanistic interpretations. Hence, less complex oviparous animal models are required, in which hypoxia can be isolated from maternal influences.