title: Sex differences in the fetal programming of hypertension.
abstract: BACKGROUND
  Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension.
  
  
  OBJECTIVE
  This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment.
  
  
  METHODS
  This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension.
  
  
  RESULTS
  The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males.
  
  
  CONCLUSIONS
  Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Grigore
authors.forename: Norma B
authors.initials: NB
authors.lastname: Ojeda
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Alexander
mesh_terms: D000818:Animals; D001724:Birth Weight / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D002908:Chronic Disease; D004958:Estradiol / Q000502:physiology; D005260:Female; D005333:Fetus / Q000503:physiopathology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D044342:Malnutrition / Q000503:physiopathology; D023421:Models, Animal; D010927:Placental Insufficiency / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000502:physiology; D012737:Sex Factors
chemical_list: D012739:Gonadal Steroid Hormones; D004958:Estradiol