An adverse foetal environment is associated with increased risk of cardiovascular,
metabolic, neuroendocrine and psychological disorders in adulthood. Exposure to stress
and its glucocorticoid hormone mediators may underpin this association. In humans
and in animal models, prenatal stress, excess exogenous glucocorticoids or inhibition
of 11β-hydroxysteroid dehydrogenase type 2 (HSD2; the placental barrier to maternal
glucocorticoids) reduces birth weight and causes hyperglycemia, hypertension, increased
HPA axis reactivity, and increased anxiety-related behaviour. Molecular mechanisms
that underlie the 'developmental programming' effects of excess glucocorticoids/prenatal
stress include epigenetic changes in target gene promoters. In the case of the intracellular
glucocorticoid receptor (GR), this alters tissue-specific GR expression levels, which
has persistent and profound effects on glucocorticoid signalling in certain tissues
(e.g. brain, liver, and adipose). Crucially, changes in gene expression persist long
after the initial challenge, predisposing the individual to disease in later life.
Intriguingly, the effects of a challenged pregnancy appear to be transmitted possibly
to one or two subsequent generations, suggesting that these epigenetic effects persist.
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