Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction.
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.


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.


CONCLUSIONS
The results suggest that IUGR induces cardiac dysfunction and permanent changes on the sarcomere.
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Iratxe
I
Torre
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Anna
A
González-Tendero
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Physense, Departament de Tecnologies de la Informació i les Comunicacions (DTIC), Universitat Pompeu Fabra, Barcelona, Spain.
Patricia
P
García-Cañadilla
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Fátima
F
Crispi
Bioinformatics Department, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain; Functional Genomics Node, INB, CIPF, Valencia, Spain.
Francisco
F
García-García
ICREA, Universitat Pompeu Fabra, Barcelona, Spain.
Bart
B
Bijnens
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Igor
I
Iruretagoyena
Bioinformatics Department, Centro de Investigación Principe Felipe (CIPF), Valencia, Spain; Functional Genomics Node, INB, CIPF, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), CIPF, Valencia, Spain.
Joaquin
J
Dopazo
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Ivan
I
Amat-Roldán
BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain.
Eduard
E
Gratacós
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005318:Fetal Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005333:Fetus / Q000503:physiopathology*; D020869:Gene Expression Profiling; D009929:Organ Size; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits; D012518:Sarcomeres / Q000000981:diagnostic imaging*
D015415:Biomarkers