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BioMed Research International
Volume 2014, Article ID 280497, 11 pages
http://dx.doi.org/10.1155/2014/280497
Research Article

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

1Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367/Interior, 4° Piso, 8330024 Santiago, Chile
2Departamento de Gastroenterología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367/Interior, 4° Piso, 8330024 Santiago, Chile
3Departamento de Nefrología y Centro de Investigaciones Médicas, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 44, 2° Piso, 8330024 Santiago, Chile
4Centro de Nutrición Molecular y Enfermedades Crónicas, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Avenida Bernardo O’Higgins 340, 8331150 Santiago, Chile

Received 31 March 2014; Revised 23 May 2014; Accepted 20 June 2014; Published 10 September 2014

Academic Editor: Luis Sobrevia

Copyright © 2014 Dolores Busso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.