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.

Cardiovascular Diseases of Developmental Origins: Preventive Aspects of Gut Microbiota-Targeted Therapy

“…As Table 1 illustrates, the rat is the most common species used. The possible reason might be that rat models provide a low-cost option with a short life cycle that is easy to handle [ 53 , 54 ]. Although other species, such as rabbits, sheep, and pigs, are used in DOHaD research [ 53 , 54 ], limited information is provided on using large animals to study gut microbiota and the developmental origins of CVD.…”

“…Presently, several mechanisms have been linked to the developmental origins of CVD, such as oxidative stress, nitric oxide (NO) deficiency, dysregulated nutrient-sensing signals, gut microbiome dysbiosis, epigenetic regulation, sex differences, etc. [ 2 , 14 , 20 , 21 , 22 , 54 ]. Some of them are interrelated to gut microbiota dysbiosis.…”

Perinatal Resveratrol Therapy to Dioxin-Exposed Dams Prevents the Programming of Hypertension in Adult Rat Offspring

“…Although similar pattern of BP-lowering effect by resveratrol was obtained in the TCDD as well as in the DEX + TCDD model, these findings suggest the protective mechanism of resveratrol may differ between the one-hit and two-hit model. Among several mechanisms proposed behind programming of hypertension, renal inflammation represents a key pathophysiological process [4][5][6][7][8]. Pro-inflammatory cytokines contribute to a state of persistent low-grad inflammation.…”

“…More and more evidence is emerging highlighting the important role of renal programming in the development of hypertension [ 4 , 5 , 6 , 7 ]. A wide variety of maternal insults can affect developing kidney, resulting in renal programming and consequently adulthood hypertension [ 8 ]. These include maternal undernutrition, overweight, maternal illness, drug use, infection, inflammation, exposure to environmental chemicals, etc.…”

“…These include maternal undernutrition, overweight, maternal illness, drug use, infection, inflammation, exposure to environmental chemicals, etc. [ 8 ]. Many studies have reported the adverse effects that occur in later life following exposure to environmental chemicals during kidney development [ 9 ].…”