Prenatal placental and postnatal mammary programming of cardiovascular and renal diseases

Funded Activity Summary

Being born small and the associated catch-up growth, independently predict adult hypertension. Reduced placental blood flow is a major cause of fetal growth restriction and is implicated in programming adult disease. We are the first to demonstrate that placental compromise in rats also adversely affects breast development, milk quality and supply, which further impair growth during lactation. This is followed by accelerated growth after weaning, programming more adverse outcomes. Using a rat model, we will determine for the first time if restricted nutrition before birth via the placenta or after birth via lactation increases the risk of developing high blood pressue and kidney and blood vessel dysfunction. Manipulations of nutrition after birth will be achieved by cross-fostering studies. We will establish whether a reduction in the number of functioning units (nephrons) in the kidney, alterations in key genes involved in kidney development and changes in blood vessel reactivity are associated with developing hypertension. We will manipulate the renin-angiotensin system (RAS), which is important in determining kidney function, to define its role in hypertension in this model. We propose that a common lifestyle insult, such as modest elevation in dietary salt, will evoke exaggerated responses in adult offspring who were born small. These studies will identify the mechanisms by which the kidney, vasculature and RAS contribute to the programming of hypertension and the relative roles of the prenatal and postnatal environments. Defining the underlying mechanisms responsible will provide insight into early life interventions that may lessen these adverse consequences for longer-term health. Identification of critical periods after birth, rather than before, would offer a greater likelihood that practical public health interventions can be developed to improve adult health in this emerging field.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $503,776.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Foetal Development and Medicine

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Childhood growth | Early origins of disease | Hypertension | Kidney | Low birth weight | Placenta | Renal disease

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