237 CARDIOMYOCYTE NUMBER AND EXPRESSION OF FATTY ACID β-OXIDATIVE GENES ARE DIFFERENTIALLY AFFECTED BY THE CAUSE OF FETAL GROWTH RESTRICTION AND SEX

Abstract

Background: Fetal growth restriction (FGR) is associated with an increased risk of cardiovascular disease (CVD) in adulthood and this may be due to reduced number and/or altered metabolism of cardiomyocytes. We hypothesise that FGR due to reduced maternal oxygen (MH) and/or nutrition (MNR) will decrease cardiomyocyte number and increase expression of FAO genes in offspring. Method: Date-mated guinea pigs at 35d gestation (term, 69d) were assigned to Control (21% O2; food ad libitum, n=16), MH (12% O2; food ad libitum, but ate less, n=11) or MNR (21% O2; food weight matched to MH, n=9). The heart of offspring was collected at 120d of age and total number of cardiomyocytes and mRNA expression of genes involved in transport, activation and oxidation of FAs was determined by stereological techniques and real time RT-PCR in the left ventricle (LV), respectively. Data was analysed by two-way ANOVA for Treatment and Sex and by Duncan post-hoc tests. Results: MH and MNR reduced birth weight, but did not affect adult body or LV weight. In females, MH reduced the number of cardiomyocytes and MNR increased expression of long chain acyl-CoA dehydrogenase, however, in males MH and MNR decreased expression of AMPK. Conclusion: These data suggest FGR may lead to increased vulnerability to CVD in females due to decreased cardiomyocyte number if the FGR was due to MH, but greater cardiac FAO if the FGR was due to MNR. In contrast, male offspring exposed to MH and MNR may have decreased cardiac FAO in adulthood.