ReviewThe role of prenatal stress in the etiology of developmental behavioural disorders
Section snippets
Stress response
Animals react to stress by mobilizing energy stores in preparation for a brief surge of enhanced activity (‘flight or fight’). The stress response is mediated by a sequence of neurological and endocrine messages involving the secretion of corticotropin releasing factor (CRF) and arginine vasopressin (AVP) by the paraventricular nucleus (PVN) of the hypothalamus, which in turn stimulate the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary lobe. ACTH stimulates release of
Hormonal responses to prenatal stress throughout the life span
A range of stressors has been used in rodent studies of PS. Mild to moderate stressors include exposing the pregnant dam to saline injections, or unpredictable noise, whereas more severe stress entails daily restraint stress, cold water immersion, or electric shock to the tail. The time-course of the hormonal sequelae of PS has not been fully elucidated. CORT and ACTH were elevated in the hypothalami of foetuses of both sexes following treatment of the pregnant dam with either restraint stress
PS-induced structural modification of limbic structures in brain
Limbic structures involved in regulation of the stress response are particularly vulnerable to stress in adults, as evidenced by the reduction in hippocampal volume in patients with post-traumatic stress disorder (PTSD) [14] and in monkeys who had been exposed to severe social stress and drastic weight loss [123]. Although changes in hippocampal volume in primates following PS have not been reported, Uno et al. [122] reported that prenatal administration of dexamethasone to pregnant rhesus
Effect of PS on behavioural measures
Several developmental measures have been studied in relation to PS, including motor development, body weight and developmental milestones, immune system, cardiovascular health, sexual development and behaviour [20], [131]; however, this review will focus only on some aspects of locomotion, learning, and reactivity to stress in PS offspring.
Mediation of PS effects by maternal CORT
There is substantial evidence that endogenous GCs mediate some of the changes in HPA responsiveness in PS offspring both in rodents and primates [69]. Administration of exogenous GCs to the pregnant dam mimics the effects of PS and conversely, adrenalectomy (ADX) counteracts the effects of PS.
Foetuses are protected to some extent from circulating maternal GCs by placental 11β-HSD type 2 [69], [133]. This enzyme has less activity for synthetic than for endogenous GCs, which may account for the
PS in non-human primates: effects on hormonal response, neurotransmitters and behaviour
Primate brain development differs from that of rodents in that much of the neuroendocrine maturation occurs in utero [69]. This suggests that the time course for the effects of PS on development may be different. Thus, it is critical to demonstrate that the behavioural effects of PS can be demonstrated in primate species. The studies of PS in several primate species suggest that social and emotional stressors can affect the behavioural and motor development of offspring. Because the stressed
Developmental sequelae to steroid administration in pregnancy
One approach to this issue has been to examine the effects of exogenous steroids on birth outcome and later development. Since synthetic corticoids, such as dexamethasone, are not easily metabolized and may cross the placental barrier more readily than cortisol [133], they are liable to affect intellectual and social development. Exogenous steroids are routinely administered to pregnant women whose foetuses are diagnosed with congenital adrenal hyperplasia (CAH) or to women who are expected to
Acknowledgements
The author thanks the anonymous referee for helpful comments on the manuscript.
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