Sex differences in developmental origins of cardiovascular disease

The developmental origins of health and disease (DOHaD) theory posits that suboptimal environments in utero and/or early postnatal life can cause structural and functional changes in key organ systems, thereby predisposing the individual to chronic disease in later life. Epidemiological, clinical, and preclinical studies show that the cardiovascular, metabolic, and neuroendocrine systems of the offspring can be influenced by environmental factors per se, or maternal responses to such stressors during development. Many studies have also uncovered differences between males and females in the nature, severity, and timing of such perturbations. This chapter provides a summary of the developmental programming of cardiovascular dysfunction and discusses evidence for sex-based differences therein. To begin, epidemiological studies that provided the foundations for the DOHaD theory are discussed, followed by a brief summary of animal models of perinatal stress currently in use; finally, this chapter presents an updated overview of the sex differences in mechanisms underlying the programming of cardiovascular disease.