The ontogeny of genes related to ovine fetal cardiac growth

Abstract

The objective of this study was to determine the ontogenetic profiles in left and right ventricle of genes implicated in cardiac growth, including mineralocorticoid (MR) and glucocorticoid (GR) receptor, 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and 2 and genes of the angiotensin system and insulin-like growth factor (IGF) family. Samples from left and right ventricles (LV, RV) were collected from hearts of sheep fetuses at 80, 100, 120, 130, and 145 days of gestation and from newborn lambs. Quantitative real-time PCR was performed to determine the MR, GR, 11beta-HSD 1 and 2, angiotensin converting enzyme (ACE) 1 and 2, IGF1, IGF2, IGF receptors IGF-1R and IGF-2R, and IGF-binding proteins (IGFBP) 2 and 3. In the LV, MR and GR both decreased toward term. In the RV, MR and GR expression did not decrease, but both 11beta-HSD 1 and 2 mRNA levels increased after birth. ACE1 expression in LV and RV sharply increases just before parturition, whereas ACE2 decreased in the LV and RV in late gestation. IGF2, IGF2R, and IGFBP2 expression levels substantially decreased in late gestation in LV and RV; IGF2R also decreased with age in LV. These patterns suggest that reduced expression of genes related to IGF and angiotensin II action occur as proliferative activity declines and terminal differentiation occurs in the late gestation fetal heart.

Fig. 1

Expression of mRNA for MR, GR, 11β-HSD1, and 11β-HSD2 in left ventricles of 80, 100, 120, 130, and 145 day fetuses and postnatal lambs (pn) and in right ventricles of 80, 100, 130, 145 and postnatal lambs. Data are depicted as mRNA fold changes relative to 80d calculated using the expression 2^ˆ−ΔΔCt and expressed as a mean fold change ±SEM. Letters indicate significant differences (p < 0.05) a: 80d, b: 100d, c:120d, d: 130d, f: 145d, g: newborn.

Fig. 2

Expression of mRNA for IGF1, IGF2, IGF1R, IGF2R and IGFBP2 from left and right ventricles of fetal and newborn lambs. IGFBP3 were measured in left ventricle only. Ages and significance are as indicated in legend to (Fig. 1).

Fig. 3

Expression of mRNA for Angiotensinogen, AT1R, AT2R, ACE1 and ACE2 in left and right ventricles of fetal and newborn lambs. Ages and significance are as indicated in legend to (Fig. 1).