Testosterone is involved in mediating the effects of prenatal stress in male guinea pig offspring

摘要

A link exists between stress during pregnancy and altered hypothalamic–pituitary–adrenal (HPA) activity and behaviour in children. In the guinea pig, male offspring born to mothers that were exposed to stress during pregnancy demonstrated increased anxiety, basal cortisol levels and decreased testosterone concentrations. Testosterone is known to inhibit HPA function and anxiety behaviours. Therefore, we hypothesized that restoring plasma testosterone would ameliorate the differences observed in HPA function and behaviour. Pregnant guinea pigs were exposed to a stressor during the period of rapid fetal brain growth (prenatal stress, PS) or left undisturbed (control, C). Behaviour in an open-field and prepulse inhibition (PPI) of the acoustic startle reflex (ASR) was assessed in juvenile offspring. In adulthood, male offspring were divided into four groups: Control + sham gonadectomy (GDX), control + GDX + testosterone replacement, PS + sham GDX and PS + GDX + testosterone. Male offspring were retested in the open-field and PPI. Basal HPA activity was also assessed. As juveniles, PS males exhibited significantly lower ASR (P < 0.05) and elevated PPI. In adulthood, PS male offspring exhibited significantly decreased PPI (P < 0.02) and this was reversed by administration of testosterone. We also found that adult PS offspring exhibited significantly less activity in the open-field (P < 0.05) and administration of testosterone increased ambulatory activity in PS animals. Basal plasma adrenocorticotrophin hormone (ACTH) levels were significantly greater in PS animals and there was a trend towards reversal by administration of testosterone in PS males. In conclusion, prenatal stress results in male guinea pig offspring that exhibit age-dependent differences in ambulatory activity, sensorimotor gating and HPA activity. In adulthood, the behavioural changes are reversed by replacement of plasma testosterone.