Long‐term Effects of Prenatal Stress and Glucocorticoid Exposure

Abstract

There is a growing body of evidence suggesting that events during prenatal life can have long-lasting effects on development and adult health. Stress during pregnancy is common and has been linked to increased incidence of a range of affective and behavioral outcomes in the offspring in later life and also some somatic outcomes. Glucocorticoids, and their actions on the fetus, which are regulated by placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), are hypothesized to mediate these effects. Animal studies have demonstrated long-term effects of stress and glucocorticoid administration on behavioral outcomes, as well as increased blood pressure, altered hypothalamic pituitary adrenal axis (HPA) function, and decreased glucose tolerance and brain size. In humans, licorice, which inhibits placental 11β-HSD2 when consumed during pregnancy, has been shown to increase the risk of behavioral problems linked to altered HPA activity. Synthetic glucocorticoids administered during pregnancy to improve fetal lung maturity in threatened preterm birth have been shown to reduce birth weight and head circumference, but have not been linked to gross changes in long-term health to date. It is important to consider the long-term consequences of stress, and medication that mimics stress, during pregnancy.

Maternal Stress Affects Fetal Growth but Not Developmental Instability in Rabbits

“…These observations are in agreement with studies in rabbits showing that reductions in maternal body weight can result in lowered fetal weight and transient alterations in ossification, representing a delay in development associated with growth retardation [37]. Also, food shortage generally increases baseline glucocorticoids [40,41] and in mammals' cortisol passing the placental barrier is considered a primary origin of prenatal stress [41]. Hence, it can be hypothesized that a change in feeding regime or body weight gain may influence DI and result in higher FA levels and/or fPD through the action of glucocorticoids.…”

Stress, ageing and their influence on functional, cellular and molecular aspects of the immune system

“…Long-term effects seem to emerge not only after negative maternal behaviours, such as poor prenatal nutrition, but also following external, psychological and environmental stress in mothers (reviewed in Graham et al 2006). For example, early life stress through the excess of maternal stress hormones, mainly GC (Painter et al 2012), has been shown to relate to emotional problems and learning deficits, and it could lead to conditions such as type 2 diabetes and general depression and anxiety symptoms in adulthood (Weinstock 2008).…”

The postnatal origin of adult neural stem cells and the effects of glucocorticoids on their genesis

“…Although glucocorticoids are essential for normal brain development, exposure of the fetal brain to an excess of glucocorticoids can also modify fetal brain development and permanently alter the function of the hypothalamic pituitary adrenal axis (HPA) in postnatal life [23][24][25]. There is evidence suggesting that events during prenatal life have longlasting effects during postnatal development and in the adult, for example altering the regulation of the HPA, increasing blood pressure and/or impairing glucose tolerance in the brain [26]. Indeed, it is known that prenatal glucocorticoids enhance the vulnerability to environmental toxicants [27] and furthermore, in the fetus glucocorticoids are thought to affect a range of affective and behavioral outcomes in the offspring in later life, as well as producing some somatic outcomes [26].…”

“…There is evidence suggesting that events during prenatal life have longlasting effects during postnatal development and in the adult, for example altering the regulation of the HPA, increasing blood pressure and/or impairing glucose tolerance in the brain [26]. Indeed, it is known that prenatal glucocorticoids enhance the vulnerability to environmental toxicants [27] and furthermore, in the fetus glucocorticoids are thought to affect a range of affective and behavioral outcomes in the offspring in later life, as well as producing some somatic outcomes [26].…”