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Departments of
1 Physiology
2 Obstetrics and Gynaecology
3 Medicine, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
Prenatal stress can have profound long-term influences on physiological function throughout the course of life. We hypothesized that focused periods of moderate prenatal stress at discrete time points in late gestation have differential effects on hypothalamo–pituitary–adrenal (HPA) axis function in adult guinea pig offspring, and that changes in HPA axis function will be associated with modification of anxiety-related behaviour. Pregnant guinea pigs were exposed to a strobe light for 2 h on gestational days (GD) 50, 51, 52 (PS50) or 60, 61, 62 (PS60) (gestation length 
70 days). A control group was left undisturbed throughout pregnancy. Behaviour was assessed in male offspring on postnatal day (PND)25 and PND70 by measurement of ambulatory activity and thigmotaxis (wall-seeking behaviour) in a novel open field environment. Subsequent to behavioural testing, male offspring were cannulated (PND75) to evaluate basal and activated HPA axis function. Body weight was significantly decreased in adult PS50 and PS60 offspring and this effect was apparent soon after weaning. The brain-to-body-weight ratio was significantly increased in adult PS50 males. Basal plasma cortisol levels were elevated in PS50 male offspring throughout the 24 h sampling period compared with controls. In response to an ACTH challenge and to exposure to an acute stressor, PS60 male offspring exhibited elevated plasma cortisol responses. Plasma testosterone concentrations were strikingly decreased in PS50 offspring. Thigmotaxis in the novel environment was increased in PS50 male offspring at PND25 and PND70, suggesting increased anxiety in these animals. In conclusion, prenatal stress during critical windows of neuroendocrine development programs growth, HPA axis function, and stress-related behaviour in adult male guinea pig offspring. Further, the nature of the effect is dependant on the timing of the maternal stress during pregnancy.
(Received 10 May 2005;
accepted after revision 27 May 2005;
first published online 2 June 2005)
Corresponding author S.G. Matthews: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, M5S 1A8. Canada. Email: stephen.matthews{at}utoronto.ca
This article has been cited by other articles:
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  A. Kapoor, J. Leen, and S. G. Matthews Molecular regulation of the hypothalamic-pituitary-adrenal axis in adult male guinea pigs after prenatal stress at different stages of gestation J. Physiol., September 1, 2008; 586(17): 4317 - 4326. [Abstract] [Full Text] [PDF]
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C. Bertram, O. Khan, S. Ohri, D. I. Phillips, S. G. Matthews, and M. A. Hanson Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function J. Physiol., April 15, 2008; 586(8): 2217 - 2229. [Abstract] [Full Text] [PDF]
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D. I. W. Phillips and A. Jones Fetal programming of autonomic and HPA function: do people who were small babies have enhanced stress responses? J. Physiol., April 1, 2006; 572(1): 45 - 50. [Abstract] [Full Text] [PDF]
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A. Kapoor, E. Dunn, A. Kostaki, M. H. Andrews, and S. G. Matthews Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids J. Physiol., April 1, 2006; 572(1): 31 - 44. [Abstract] [Full Text] [PDF]
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