Endocrine Abstracts (2009) 19 S11

Transgenerational effects of glucocorticoid programming

A Drake

University of Edinburgh, Edinburgh, UK.

Epidemiological studies have demonstrated an association between low birth weight and an increased prevalence of cardio-metabolic disorders in later life. Both human and animal studies suggest that this phenomenon of ‘early life programming’ is not limited to the first generation offspring. Epidemiological studies in humans have shown intergenerational effects on birth weight, cardiovascular risk factors and type 2 diabetes. Transgenerational effects on birth weight, glucose tolerance, blood pressure and the hypothalamic–pituitary–adrenal axis have also been reported in animal models.

One of the potential mechanisms underpinning early life programming is that of exposure to excess glucocorticoids in early life which may influence development and have long-term consequences. Using a rodent model of programming in which fetal overexposure to excess glucocorticoid results in reduced birth weight, increased expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and adult hyperglycaemia, we have shown that dexamethasone exposure can have intergenerational effects on birth weight, PEPCK and glucose tolerance and crucially, that these effects can be transmitted by either maternal or paternal lines.

This intergenerational transmission of programming effects, which can be passed through both maternal and paternal lines indicates the likely importance of epigenetic factors in the intergenerational inheritance of the ‘programming phenotype’ and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.

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