Dietary restriction in the periconceptional period in normal-weight or obese ewes results in increased abundance of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R methylation in the adrenal of the offspring

Abstract

Exposure to dietary restriction during the periconceptional period in either normal or obese ewes results in increased adrenal growth and a greater cortisol response to stress in the offspring, but the mechanisms that programme these changes are not fully understood. Activation of the angiotensin type 1 receptor (AT1R) has been demonstrated to stimulate adrenal growth and steroidogenesis. We have used an embryo transfer model in the sheep to investigate the effects of exposure to dietary restriction in normal or obese mothers from before and 1 week after conception on the methylation status, expression, abundance and localisation of key components of the renin-angiotensin system (RAS) in the adrenal of post-natal lambs. Maternal dietary restriction in normal or obese ewes during the periconceptional period resulted in an increase in angiotensin-converting enzyme (ACE) and AT1R abundance in the absence of changes in the methylation status or mRNA expression of ACE and AT1R in the adrenal of the offspring. Exposure to maternal obesity alone also resulted in an increase in adrenal AT1R abundance. There was no effect of maternal dietary restriction or obesity on ACE2 and AT2R or on ERK, calcium/calmodulin-dependent kinase II abundance, and their phosphorylated forms in the lamb adrenal. Thus, weight loss around the time of conception, in both normal-weight and obese ewes, results in changes within the intra-adrenal RAS consistent with increased AT1R activation. These changes within the intra-adrenal RAS system may contribute to the greater adrenal stress response following exposure to signals of adversity in the periconceptional period.

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

“…In addition to in vitro ART, a sub-optimal uterine environment following embryo transfer is thought to further influence the long-term viability of offspring. Interestingly, factors that create an adverse interuterine environment, including maternal high-salt diet, inflammation, and dietary restriction, have also been shown to alter the fetal and offspring RAS [57][58][59][60].…”

Development of an experimental model of maternal allergic asthma during pregnancy

“…, ; Zhang et al . ), cortisol availability (GR, MR, 11βHSD1 and 11βHSD2; Gentili et al . ), inflammation (TNFα and IL1β), fibrosis (TGFβ, collagen type II, MMP 2, TIMP 1, TIMP 2 and TIMP 3; Zhang et al .…”

“…The reference genes (β actin, hypoxanthine phosphoribosyltransferase 1 and tyrosine 3-monooxygenase (YWAHZ)) were chosen (Duffield et al 2009;Passmore et al 2009;Wang et al 2013;Hellemans & Vandesompele, 2014) based on expression analysis using the geNorm component of the qBase (Biogazelle, Zwinjnaarde, Belgium) relative quantification analysis software (Hellemans et al 2007) because their expression was stable across samples (maximum value, factor = 0.3-0.4; Vandesompele et al 2002;Soo et al 2012;Hellemans & Vandesompele, 2014). The relative expression of messenger ribonucleic acid (mRNA) transcripts of molecules involved in physiological hypertrophy (IGF1, IGF1R and IGF2; Gentili et al 2009;Zhang et al 2010), pathological hypertrophy (ANP, BNP, IGF2R and AT1R; Lie et al 2013Lie et al , 2014Zhang et al 2013), cortisol availability (GR, MR, 11βHSD1 and 11βHSD2; Gentili et al 2009), inflammation (TNFα and IL1β), fibrosis (TGFβ, collagen type II, MMP 2, TIMP 1, TIMP 2 and TIMP 3; Zhang et al 2010;Wang et al 2015), proliferation (PCNA and Ki67), reactive oxygen species (HO1) and glucose and fatty acid uptake (GLUT1, GLUT4, FATP1 and CPT1; Gentili et al 2009;Wang et al 2013;Nicholas et al 2014) were measured by quantitative real-time RT-PCR (qRT-PCR) ( Table 1) using Fast SYBR Green Master Mix (Applied Biosystems, Foster City, CA, USA) on a ViiA7 Fast Real-time PCR system (Applied Biosystems) as previously described (Wang et al 2011;Soo et al 2012;McGillick et al 2013).…”

Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life

“…DNA methylation within the AT 1 R promoter was analyzed from the left ventricle of each lamb (ABW, n = 13; LBW, n = 8) by combined bisulfite restriction assay (COBRA) (Xiong and Laird ; Zhang et al. , ; Wang et al. ).…”

“…DNA methylation within the AT 1 R promoter was analyzed from the left ventricle of each lamb (ABW, n = 13; LBW, n = 8) by combined bisulfite restriction assay (COBRA) (Xiong and Laird 1997;Zhang et al 2010Zhang et al , 2013Wang et al 2011). DNA (~2 lg) from individual hearts was subjected to bisulfite conversion (Epitect, Qiagen, Chadstone Centre, VIC, Australia).…”