Sex dimorphism in developmental programming of health and disease

Events that occur in the early fetal environment have been linked to long-term health consequences in the adult. Human and animal studies have shown that unbalanced maternal nutrition is associated with the development of cardiovascular and metabolic disease in adulthood. In the maternal low protein model, protein deprivation throughout pregnancy in rats leads to elevated blood pressure in adult offspring. This model has been extensively used to study the mechanisms that may link maternal nutrition with impaired fetal growth and later cardiovascular disease. The onset and severity of hypertension is more pronounced in males than females similar to the gender differences in the occurrence of cardiovascular diseases in humans at various stages of life. This chapter discusses how recent findings using this model throw light on sex-specific peripheral vascular mechanisms that contribute for the development of hypertension in the offspring and discuss underlying mechanisms that mediate these adaptive responses. Studies from this model demonstrate that there are sex-specific disturbances in endothelial cell associated relaxations; EDHF-related in males and nitric oxide-related in females. Vasoconstriction to angiotensin II is exaggerated, with greater potency and efficacy in males. Alteration in steroid levels, estradiol and testosterone appears to have an underlying regulatory role in the development of hypertension in this model.