title: Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring.
abstract: Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression--a transcription factor sensitive to inflammation and oxidative stress--suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.
authors.affiliation: Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago, Chile. amronco@inta.cl
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Ronco
authors.forename: Marcela
authors.initials: M
authors.lastname: Montenegro
authors.forename: Paula
authors.initials: P
authors.lastname: Castillo
authors.forename: Manuel
authors.initials: M
authors.lastname: Urrutia
authors.forename: Daniel
authors.initials: D
authors.lastname: Saez
authors.forename: Sandra
authors.initials: S
authors.lastname: Hirsch
authors.forename: Ramiro
authors.initials: R
authors.lastname: Zepeda
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Llanos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
chemical_list: D002104:Cadmium