Animal Models for DOHaD Research: Focus on Hypertension of Developmental Origins

Abstract

Increasing evidence suggests that fetal programming through environmental exposure during a critical window of early life leads to long-term detrimental outcomes, by so-called developmental origins of health and disease (DOHaD). Hypertension can originate in early life. Animal models are essential for providing convincing evidence of a causal relationship between diverse early-life insults and the developmental programming of hypertension in later life. These insults include nutritional imbalances, maternal illnesses, exposure to environmental chemicals, and medication use. In addition to reviewing the various insults that contribute to hypertension of developmental origins, this review focuses on the benefits of animal models in addressing the underlying mechanisms by which early-life interventions can reprogram disease processes and prevent the development of hypertension. Our understanding of hypertension of developmental origins has been enhanced by each of these animal models, narrowing the knowledge gap between animal models and future clinical translation.

Keywords: animal model; developmental origins of health and disease (DOHaD); gut microbiota; hypertension; oxidative stress; pregnancy; renin-angiotensin system; reprogramming.

Figure 1

Schematic illustration of the selection of animal models for studying hypertension of developmental origins in adulthood according to early-life environmental insults, animal species, and common mechanisms. Lines with arrows (top section) indicate types of early-life insults produced in particular species of animals to induce hypertension in adult offspring. The study of other animals in DOHaD research (non-human primates, rabbits, pigs, etc.) is limited.

Figure 2

Overview of nutritional interventions used to modulate nutritional status during pregnancy and/or lactation to study hypertension of developmental origins in animal models. Fe = iron; Zn = zinc; Vit D = vitamin D; Na = sodium; Ca = calcium.