Environmental disturbance confounds prenatal glucocorticoid programming experiments in Wistar rats

Abstract

Abstract Low birth weight in humans is predictive of hypertension in adult life, and while the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We have previously shown that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. This current study aimed to unravel the molecular nature of this hypertension. However, unknowingly, post hoc investigations revealed that our animals had been subjected to environmental noise stresses from an adjacent construction site, which were sufficient to confound our prenatal DEX-programming experiments. This perinatal stress successfully established low birth weight, hypercorticosteronaemia, insulin resistance, hypertension and hypothalamic-pituitary -adrenal axis dysfunction in vehicle (VEH)-treated offspring, such that the typical distinctions between both treatment groups were ameliorated. The lack of an additional effect on DEX-treated offspring is suggestive of a maximal effect of perinatal stress and glucocorticoids, serving to prevent against the potentially detrimental effects of sustained glucocorticoid hyper-exposure. Finally, this paper serves to inform researchers of the potential detrimental effects of neighbouring construction sites to their experiments. As research institutions expand and respond to everchanging building and animal welfare regulations, they are required to undergo either new construction and/or renovation. However, such structural changes are associated with a plethora of nuisances, such as noise and vibration, with each disturbance being capable of powerfully stimulating the hypothalamic -pituitary -adrenal (HPA) axis. 1 The auditory system is permanently open -even during sleep. Its rapid and overshooting excitations in response to noise signals are subcortically connected, via the amygdala, to the HPA axis, resulting in corticotrophin releasing hormone and adrenocorticotrophic hormone release. 2 Animal experiments show noise-induced changes in the sensitivity of glucocorticoid receptor (GR) by increase of heat-shock proteins 3 and ultrastructural changes of the adrenal gland. 4 Increased cortisol levels have been found in humans when exposed to aircraft 5 or road traffic noise, 6 even during sleep, 7 implying these effects are mainly without mental control. Of course, increased glucocorticoid and sympathetic neural secretion is a perfect short-term stress response, coordinating appropriate metabolic and vascular changes, and thereby assisting the individual to negotiate the stressor. However, over prolonged time periods, such as persistent noise-induced stress responses, can be gravely damaging to health. 2,8 Numerous animal studies have documented the programming effects of pre-and postnatal stress on offspring physiology and behaviour, which are remarkably analogous to those induced by fetal glucocorticoid overexposure. Exposing pregnant dams to stressful stimuli results in both maternal and fetal HPA activation. 9,10 Moreover, these offspring display an activated HPA axis till weaning, as adults are more anxious and stress-responsive