Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, C42

Oral Communications

Lower fetal vitamin D status is associated with increased fetal cardiac ventricle wall thickness in the late gestation sheep

B. R. Prince1, S. A. Lanham1, C. Cooper2, R. O. Oreffo1, P. C. Calder1, N. C. Harvey2, W. D. Fraser3, M. A. Hanson1, K. R. Poore1, L. R. Green1

1. Institute of Developmental Sciences, University of Southampton, Southampton, Hants, United Kingdom. 2. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom. 3. Department of Medicine, University of East Anglia, Norwich, United Kingdom.


Epidemiological and animal studies in adulthood link vitamin D deficiency and cardiovascular function, including cardiac hypertrophy (1). The fetus is reliant on maternal vitamin D, and vitamin D deficiency affects a substantial proportion of the human population (2,3). In rodents, vitamin D deficiency in pregnancy and lactation is associated with delayed cardiac maturation and left ventricular hypertrophy in postnatal offspring (4), but could be partly contributed to by altered cardiac renin-angiotensin system activity or increased afterload postnatally. In sheep, like humans, the full complement of cardiomyocytes are formed prenatally, thus we investigated if the relationship between low vitamin D status and cardiac wall thickening already exists in fetal life. Welsh mountain ewes were fed 100% nutrient requirements (C, 2000 IU/kg vitamin D, n= 9), or a similar diet lacking the vitamin D3 supplement (VDD, 0 IU/kg vitamin D, n=10) from 17 days prior to conception until post-mortem. At 126-130 days of gestation ewes and singleton fetuses were killed (pentobarbitone overdose IV). Maternal and fetal plasma levels of the inactive 25-hydroxyvitamin-D (25(OH)-D) were measured by HPLC tandem mass spectroscopy. Fetal hearts were weighed and 3-dimensional images captured using microcomputer tomography (SkyScan 1176 Bruker microCT). Right ventricle (RV) wall thickness was assessed by in silico systematic sampling of 0.5mm2 regions (SkyScan CTAn). Data are mean±SE and were analysed by student's t-test and linear regression with 25(OH)-D (adjusted for fetal age at post-mortem). Heart weight as a percentage of body weight was not significantly different between C and VDD groups (C, 0.61±0.01 vs. VDD, 0.60±0.02 %), and was not associated with total fetal plasma levels of 25(OH)-D (all groups combined β= 0.001, p=0.299, R2=0.139). There was no significant difference in fetal RV wall thickness between C and VDD groups (C, 3.26±0.28 vs. VDD, 3.56±0.24 mm). Greater RV wall thickness was associated with lower total fetal plasma 25(OH)-D levels (β= -0.027, p=0.041, R2=0.239) and higher maternal:fetal ratio of total plasma 25(OH)-D levels (β=0.471, p=0.020, R2=0.265. Our finding that right ventricular wall thickening was associated with decreased fetal vitamin D levels (and vitamin D supply from the mother) is consistent with previous observations in postnatal rodents in response to reduced pregnancy and lactation vitamin D (4). Thus in a model with maturational similarities to humans, this suggests that the fetal heart responds to altered vitamin D supply. Such fetal cardiac structural adaptation may involve altered regulation of cardiac pro-hypertrophic genes (e.g. atrial natriuretic peptide or renin) and could have implications for combined ventricular output and blood flow distribution during fetal and subsequent postnatal life (5).

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