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J Physiol Volume 586, Number 8, 2217-2229, April 15, 2008 DOI: 10.1113/jphysiol.2007.147967
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Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function

 Caroline Bertram1, Omar Khan2, Sunil Ohri2, David I. Phillips3, Stephen G. Matthews4 and Mark A. Hanson1

1 Centre for Developmental Origins of Health and Disease, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK
2 Wessex Thoracic Centre
3 MRC Epidemiology Resource Centre, Southampton General Hospital, Southampton SO16 6YD, UK
4 Departments of Physiology, Medicine, and Obstetrics & Gynaecology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada, M5S 1A8

The perinatal environment is a powerful determinant of risk for developing disease in later life. Here, we have shown that maternal undernutrition causes dramatic changes in heart structure and hypothalamo-pituitary-adrenal (HPA) function across two generations. Pregnant guinea pigs were fed 70% of normal intake from gestational days 1–35 (early restriction; ER), or 36–70 (late restriction; LR). Female offspring (F1) were mated and fed ad libitum to create second generation (F2) offspring. Heart morphology, blood pressure, baroreceptor and HPA function were assessed in male F1 and F2 offspring. ERF1 males exhibited elevated blood pressure, increased left ventricular (LV) wall thickness and LV mass. These LV effects were maintained in the ERF2 offspring. Maternal undernutrition increased basal cortisol and altered HPA responsiveness to challenge in both generations; effects were greatest in LR groups. In conclusion, moderate maternal undernutrition profoundly modifies heart structure and HPA function in adult male offspring for two generations.

(Received 8 November 2007; accepted after revision 18 February 2008; first published online 21 February 2008)
Corresponding author S. G. Matthews: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada, M5S 1A8. Email: stephen.matthews{at}utoronto.ca






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