title: Effect of intrauterine growth restriction on the number of cardiomyocytes in rat hearts.
abstract: Epidemiologic studies have linked intrauterine growth restriction (IUGR) with an increased incidence of cardiovascular disease later in life; reduced cardiomyocyte number in IUGR hearts may underlie such prenatal programming. Our aim was to examine the effect of IUGR, as a result of maternal protein restriction, on the number of cardiomyocytes in the rat heart at birth. Rats were fed either a low-protein diet (LPD) or a normal-protein diet (NPD) during pregnancy. At birth, the offspring were killed and the hearts were immersion-fixed. The number of cardiomyocyte nuclei in the hearts were stereologically determined using an optical disector-fractionator approach. In some litters, cardiomyocytes were enzymatically isolated from freshly excised hearts and the proportion of binucleated cells was determined. Taking into account the number of binucleated cells, the nuclear counts were adjusted to estimate total cardiomyocyte number. Birth weight and heart weight were significantly reduced in the LPD offspring. This was accompanied by a significant reduction in the number of cardiomyocytes per heart in the LPD offspring compared with the NPD offspring (1.18 +/- 0.05 x 10(7) and 1.41 +/- 0.06 x 10(7), respectively; p = 0.001). The number of binucleated cardiomyocytes was low (approximately 3%) and equal in both groups. In conclusion, IUGR as a result of maternal protein restriction leads to a reduction in the number of cardiomyocytes per heart. As cardiomyocyte proliferation is rare after birth, it is plausible that this reduction in cardiomyocytes may lead to compromised cardiac function later in life.
authors.affiliation: Department of Cardiology, Leiden University Medical Centre, Leiden 2300 RC, The Netherlands.
authors.forename: Hugo Brandt
authors.initials: HB
authors.lastname: Corstius
authors.forename: Monika A
authors.initials: MA
authors.lastname: Zimanyi
authors.forename: Noori
authors.initials: N
authors.lastname: Maka
authors.forename: Thiloshini
authors.initials: T
authors.lastname: Herath
authors.forename: Walter
authors.initials: W
authors.lastname: Thomas
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Wreford
authors.forename: M Jane
authors.initials: MJ
authors.lastname: Black
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight; D002318:Cardiovascular Diseases / Q000209:etiology; D002452:Cell Count; D002467:Cell Nucleus / Q000473:pathology; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000150:complications / Q000473:pathology*; D006801:Humans; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D009929:Organ Size; D011247:Pregnancy; D051381:Rats