title: Environmental disturbance confounds prenatal glucocorticoid programming experiments in Wistar rats.
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.
authors.affiliation: Anaesthetics Department, The Royal Marsden Hospital NHS Foundation Trust, London, UK. d.oregan@imperial.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: O'Regan
authors.forename: C J
authors.initials: CJ
authors.lastname: Kenyon
authors.forename: J R
authors.initials: JR
authors.lastname: Seckl
authors.forename: M C
authors.initials: MC
authors.lastname: Holmes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000633:toxicity*; D004777:Environment; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000209:etiology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D018811:Maternal Exposure; D009622:Noise / Q000009:adverse effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D003345:Corticosterone