Implications of maternal nutrient restriction in transgenerational programming of hypertension and endothelial dysfunction across F1-F3 offspring

Author(s)

Ponzio, Beatriz Felice ^[1] ; Catelli Carvalho, Maria Helena ^[2] ; Fortes, Zuleica Bruno ^[2] ; Franco, Maria do Carmo ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP, Div Nephrol, Dept Med, EPM, BR-04023062 Sao Paulo - Brazil

^[2] Univ Sao Paulo, ICB, Inst Biomed Sci, Dept Pharmacol, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 90, n. 15-16, p. 571-577, APR 20 2012.
• Web of Science Citations: 34

Abstract

Aims: An extensive variety of prenatal insults are associated with an increased incidence of metabolic and cardiovascular disorders in adult life. We previously demonstrated that maternal global nutrient restriction during pregnancy leads to increased blood pressure and endothelial dysfunction in the adult offspring. This study aimed to assess whether prenatal exposure to nutritional insult has transgenerational effects in F-2 and F-3 offspring. Main methods: For this, female Wistar rats were randomly divided into two groups on day 1 of pregnancy: a control group fed standard chow ad libitum and a restricted group fed 50% of the ad libitum intake throughout gestation. At delivery, all animals were fed a standard laboratory chow diet. At 11 weeks of age, one female and one male from each restricted litter were randomly selected and mated with rats from another restricted litters in order to generate the F-2 offspring. The same procedure produced F-3 generation. Similarly, the rats in the control group were bred for each generation. Key Findings: Our findings show that the deleterious effects of maternal nutrient restriction to which the F-0 mothers were exposed may not be limited to the male first generation. In fact, we found that elevated blood pressure, an impaired vasodilatory response to acetylcholine and alterations in NO production were all transferred to the subsequent males from F-2 and F-3 generations. Significance: Our data show that global nutrient restriction during pregnancy results in a specific phenotype that can be passed transgenerationally to a second and third generation. (c) 2012 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 07/58044-2 - Birth weight and cardiovascular diseases: characterization of risk and genetic factors interrelation by identifying genomic imprinting mechanisms as well as genetic polymorphisms in homocysteine and eNOS pathways
• Grantee: Maria Do Carmo Pinho Franco
• Support Opportunities: Research Grants - Young Investigators Grants