Maternal dietary restriction during the periconceptional period results in an increase in adrenal growth and in the cortisol stress response in the offspring. The intraadrenal mechanisms that result in the programming of these changes are not clear. Activation of the IGF and the signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways regulate adrenal growth. We have used an embryo transfer model in sheep to investigate the impact of exposure to either dietary restriction in normal or obese mothers or to maternal obesity during the periconceptional period on adrenal growth and function in the offspring. We assessed the adrenal abundance of key signaling molecules in the IGF-I and Janus kinase/STAT/SOCS pathways including IGF-I receptor, IGF-II receptor, Akt, mammalian target of rapamycin, ribosomal protein S6, eukaryotic translation initiation factor 4E-binding protein 1, eukaryotic translation initiation factor 4E, STAT1, STAT3, STAT5, SOCS1, and SOCS3 in female and male postnatal lambs. Maternal dietary restriction in the periconceptional period resulted in the hypertrophy of the adrenocortical cells in the zona fasciculata-reticularis and an up-regulation in STAT1, phospho-STAT1, and phospho-STAT3 (Ser727) abundance and a down-regulation in IGF-I receptor, Akt, and phospho-Akt abundance in the adrenal cortex of the postnatal lamb. These studies highlight that weight loss around the time of conception, independent of the starting maternal body weight, results in the activation of the adrenal Janus kinase/STAT pathway and adrenocortical hypertrophy. Thus, signals of adversity around the time of conception have a long-term impact on the mechanisms that regulate adrenocortical growth.

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.

Abstracts e77ventricle samples were collected from the lambs at d21 for the analysis of gene and protein expression. ResultsThere was increased plasma renin activity and ANGII concentrations in LBW compared to ABW lambs. There was increased ACE2 mRNA and decreased abundance of ATR1 but no changes in abundance of ACE or ATR2 in LBW compared to ABW lambs. There was increased phospho-Akt protein and decreased capillary density in the heart of LBW lambs compared to ABW lambs. There was decreased collagen I and II mRNA expression but no evidence of cardiac remodelling or fi brosis in the LBW lambs. There was decreased FoxO1 and FoxO3a protein in the LBW lambs compared to ABW lambs, but no changes in autophagy proteins: phospho-FoxO1, phospho-FoxO3a, Beclin1, LC3B and LAMP1 was not altered in LBW lambs.Conclusion Although circulating and local cardiac RAS components were altered in LBW lambs there was no increase in fi brosis or autophagy in the heart of the LBW lamb. LBW resulted in decreased capillary density during early postnatal life and this may result in an increased risk of impaired heart function in later life.It has previously been shown that periconceptional dietary restriction in normal and overweight ewes results in increased adrenal weight and cortisol response to stress in postnatal lambs, however the mechanisms underlying these changes are not known. The activation of intraadrenal renin-angiotensin system (RAS) has been demonstrated to promote adrenal growth and steroidogenesis through angiotensin II type I receptor (AT1R) activation.Donor ewes were assigned to one of 4 nutritional treatment groups preconception: CC, 100% metabolisable energy requirement (MER) for 5 months; CR, 100%MER for 4 months followed by 70% MER for 1 month; HH, ad libitum (180% MER) for 5 months; HR, ad libitum for 4 months followed by 70%MER for 1 month. At 6-7 d post-conception, single embryos were transferred into normal weight recipient ewes. Post mortem was conducted and adrenal glands collected from lambs at 4 months of age.In females, there was a signifi cant decrease in adrenal ACE2 mRNA expression in CR and HH than CC by qRT-PCR. ACE and AT1R immunostaining intensity in both the zona glomerulosa (ZG) and zona fasciculata-reticularis (ZF-ZR) of the adrenal cortex was higher in CR and HR than CC. There was no difference in the methylation levels of the AT1R and ACE gene promoter by combined bisulphite restriction assay in the lamb adrenal.These results demonstrate that there is an activation of the intraadrenal RAS, through an increase in ACE and AT1R and a decrease in ACE2, in the adrenal cortex of offspring exposed to dietary restriction during the periconceptional period.Background Elevated blood pressure (BP) in children and adolescents increases future risk of cardiovascular disease. The study aimed to identify the prevalence of elevated BP and risk factors among children aged 3 to 18 years from Beijing.