Background: Intrauterine growth restriction (IUGR) induces fetal cardiac remodelling and dysfunction, which persists postnatally and may explain the link between low birth weight and increased cardiovascular mortality in adulthood. However, the cellular and molecular bases for these changes are still not well understood. We tested the hypothesis that IUGR is associated with structural and functional gene expression changes in the fetal sarcomere cytoarchitecture, which remain present in adulthood./nMethods and Results: IUGR was induced in New Zealand pregnant rabbits by selective ligation of the utero-placental vessels. Fetal echocardiography demonstrated more globular hearts and signs of cardiac dysfunction in IUGR. Second harmonic generation microscopy (SHGM) showed shorter sarcomere length and shorter A-band and thick-thin filament interaction lengths, that were already present in utero and persisted at 70 postnatal days (adulthood). Sarcomeric M-band (GO: 0031430) functional term was over-represented in IUGR fetal hearts./nConclusion: The results suggest that IUGR induces cardiac dysfunction and permanent changes on the sarcomere.

This study was supported by grants from Ministerio de Economia y Competitividad PN de I+D+I 2008-2011 (ref. SAF2009_08815, SAF2012-37196, and BIO2011-27069); Instituto de Salud Carlos III (ref. PI11/00051, PI11/01709, PI12/00801) cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa”; Centro para el Desarrollo Técnico Industrial (ref. cvREMOD 2009-2012) apoyado por el Ministerio de Economia y Competitividad y Fondo de inversión local para el empleo, Spain; The Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); Obra Social “La Caixa” (Spain); Fundació Mutua Madrileña (Spain); Fundació Agrupació Mutua (Spain); AGAUR 2009 SGR grant n° 1099; and Red Temática de Investigación Cooperativa en cancer (ref. RD06/0020/1019). I.T. was supported by a post-doctoral fellowship from Carlos III Institute of Health, Spain (CD08/00176) during the time these studies were performed. P.G.C. acknowledges grant support to the Programa de Ayudas Predoctorales de Formación en Investigación en Salud del Instituto Carlos III, Spain (FI12/00362). A.G.T. was supported by an IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) pre-doctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.