Abstract
The obesity epidemic has led to more women entering pregnancy overweight or obese. In addition to adverse short-term outcomes, maternal obesity and/or gestational diabetes predispose offspring to developing obesity, type 2 diabetes and cardiovascular disease in adulthood through developmental programming. Human epidemiological studies, although vital in identifying associations, are often unable to address causality and mechanistic studies can be limited by the lack of accessibility of key metabolic tissues. Furthermore, multi-generational studies take many years to complete. Integration of findings from human studies with those from animal models has therefore been critical in moving forward this field that has been termed the 'Developmental Origins of Health and Disease'. This review summarises the evidence from animal models and highlights how animal models provide valuable insight into the maternal factors responsible for developmental programming, potential critical developmental windows, sexual dimorphism, molecular mechanisms and age-related offspring outcomes throughout life. Moreover, we describe how animal models are vital to explore clinically relevant interventions to prevent adverse offspring outcomes in obese or glucose intolerant pregnancy, such as antioxidant supplementation, exercise and maternal metformin treatment.
Highlights
MATERNAL OBESITYHuman epidemiology studies are vital in identifying associations between intrauterine insults and long-term offspring outcome
The obesity epidemic has led to more women entering pregnancy overweight or obese
Epidemiological studies show that maternal obesity during pregnancy is associated with risk of offspring developing obesity, type 2 diabetes and cardiovascular disease later in life
Summary
Human epidemiology studies are vital in identifying associations between intrauterine insults and long-term offspring outcome. Species used to study developmental programming include rodents, sheep and to a lesser extent non-human primates The latter are most closely related to humans, but their gestation period is long and they are expensive to maintain.[2] Sheep are used for their similarities to humans with respect to maturity at birth as well as the ability to carry out complex foetal physiology studies.[4,5] rodent models are often preferred due to their relatively short gestation and lifespan allowing experiments across the life-course. Genetic models of obesity can be used, such as the Leprdb/+ model, where
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