The highs and lows of programmed cardiovascular disease by developmental hypoxia: studies in the chicken embryo

Abstract

It is now established that adverse conditions during pregnancy can trigger a fetal origin of cardiovascular dysfunction and/or increase the risk of heart disease in later life. Suboptimal environmental conditions during early life that may promote the development of cardiovascular dysfunction in the offspring include alterations in fetal oxygenation and nutrition as well as fetal exposure to stress hormones, such as glucocorticoids. There has been growing interest in identifying the partial contributions of each of these stressors to programming of cardiovascular dysfunction. However, in humans and in many animal models this is difficult, as the challenges cannot be disentangled. By using the chicken embryo as an animal model, science has been able to circumvent a number of problems. In contrast to mammals, in the chicken embryo the effects on the developing cardiovascular system of changes in oxygenation, nutrition or stress hormones can be isolated and determined directly, independent of changes in the maternal or placental physiology. In this review, we summarise studies that have exploited the chicken embryo model to determine the effects on prenatal growth, cardiovascular development and pituitary-adrenal function of isolated chronic developmental hypoxia.

Keywords: IUGR; cardiovascular disease; fetus; hypoxia; programming.

Figure 1. Fetal growth in the chicken embryo at day 19–20 of incubation

Values are mean ± SEM at day 19–20 of absolute embryo weight (A), relative embryo weight (B), and brain weight relative to body weight (C) of chicken embryos incubated in either normoxia (N, n = 21) or hypoxia (H, n = 20) for isobaric hypoxia studies, and normoxia at sea level (N, n = 31) or hypoxia at high altitude (H, n = 16) for hypobaric hypoxia studies. ^*Significantly (P < 0.05) different from corresponding control. Data adapted from Giussani et al. (2007), Salinas et al. (2010) and Itani et al. (2016, 2017).

Figure 2. Comparison of the key stages of cardiac development in different animal models

Bars represent the proportion (%) of development. Roman and Arabic numerals refer to human Carnegie stage (Streeter horizons), chick Hamburger and Hamilton stage, rat and mouse embryonic days. Term: human, 38 weeks; chick, 21 days; rat, 21 days; mouse, 19 days. While the main anatomical development of the heart is complete in the rat and mouse by day 16 and 14.5, respectively, the acquisition of mature septum, valves and tendinea cords is not yet complete until after birth (Marcela et al. 2012). Drawn from data provided in Sissman (1970) and Marcela et al. (2012).

Figure 3. Aortic morphology in the chicken embryo at day 19–20 of incubation

Values are mean ± SEM at day 19–20 of wall:lumen area ratio of chicken embryos incubated in either normoxia (N, n = 10) or hypoxia (H, n = 10) for isobaric hypoxia studies, and normoxia at sea level (N, n = 8) or hypoxia at high altitude (H, n = 7) for hypobaric hypoxia studies. ^*Significantly (P < 0.05) different from corresponding control. Data adapted from Salinas et al. (2010) and Itani et al. (2016).