O'Regan, D., Kenyon, C. J., Seckl, J. R., Holmes, M. C. (2010) Environmental disturbance confounds prenatal glucocorticoid programming experiments in Wistar rats. LABORATORY ANIMALS, 44 (3). pp. 199-205. ISSN 0023-6772

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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.

Item Type:	Article
All Authors:	O'Regan, D., Kenyon, C. J., Seckl, J. R., Holmes, M. C.
Uncontrolled Keywords:	Construction; environment; glucocorticoid; programming; refinement;BLOOD-PRESSURE; ADULT HYPERTENSION; FEMALE RATS; EXPOSURE; STRESS; SYSTEM; DEXAMETHASONE; HYPERGLYCEMIA; EXPRESSION; ORIGINS
Funding Acknowledgement:	Wellcome Trust ; Medical Research Council
Funding Text:	Expert animal assistance was provided by Mr Willy Mungall. This study was supported by a Wellcome Trust CVRI studentship (DO'R), the Wellcome Trust (JRS and MCH) and the Medical Research Council (CJK).
Research teams:	Clinical Units > Other Royal Marsden Services/Clinical Units
Depositing User:	Users 10 not found.
Date Deposited:	16 Aug 2010 10:17
Last Modified:	16 Aug 2010 10:17
URI:	http://publications.icr.ac.uk/id/eprint/9811

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