title: Heart disease link to fetal hypoxia and oxidative stress.
abstract: The quality of the intrauterine environment interacts with our genetic makeup to shape the risk of developing disease in later life. Fetal chronic hypoxia is a common complication of pregnancy. This chapter reviews how fetal chronic hypoxia programmes cardiac and endothelial dysfunction in the offspring in adult life and discusses the mechanisms via which this may occur. Using an integrative approach in large and small animal models at the in vivo, isolated organ, cellular and molecular levels, our programmes of work have raised the hypothesis that oxidative stress in the fetal heart and vasculature underlies the mechanism via which prenatal hypoxia programmes cardiovascular dysfunction in later life. Developmental hypoxia independent of changes in maternal nutrition promotes fetal growth restriction and induces changes in the cardiovascular, metabolic and endocrine systems of the adult offspring, which are normally associated with disease states during ageing. Treatment with antioxidants of animal pregnancies complicated with reduced oxygen delivery to the fetus prevents the alterations in fetal growth, and the cardiovascular, metabolic and endocrine dysfunction in the fetal and adult offspring. The work reviewed offers both insight into mechanisms and possible therapeutic targets for clinical intervention against the early origin of cardiometabolic disease in pregnancy complicated by fetal chronic hypoxia.
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK, dag26@cam.ac.uk.
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
authors.forename: Youguo
authors.initials: Y
authors.lastname: Niu
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.forename: Hans G
authors.initials: HG
authors.lastname: Richter
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Camm
authors.forename: Avnesh S
authors.initials: AS
authors.lastname: Thakor
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kane
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hansell
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Brain
authors.forename: Katie L
authors.initials: KL
authors.lastname: Skeffington
authors.forename: Nozomi
authors.initials: N
authors.lastname: Itani
authors.forename: F B Peter
authors.initials: FB
authors.lastname: Wooding
authors.forename: Christine M
authors.initials: CM
authors.lastname: Cross
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Allison
mesh_terms: D005260:Female; D005311:Fetal Hypoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology