High expression of adrenal cortisol synthases is acquired after intrauterine inflammation in periviable sheep fetuses
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PROVIDER: PRJNA958165 | ENA |
REPOSITORIES: ENA
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Project description:To clarify the effects of endotoxin-induced intrauterine inflammation on the HPA axis of periviable sheep fetuses, fetal sheep (0.63 term) were divided into two groups: (1) the endotoxin group, in which the endotoxin was injected into the amniotic fluid and (2) the control group, in which the saline solution was injected instead. Gene expression levels in the fetal adrenal glands of each group were analyzed by RNA-seq.
2023-07-28 | GSE230267 | GEO
Project description:We performed mRNA-seq of a PRKACA-mutant adrenal tumor and demonstrated that the mutation is expressed at the mRNA level. Total RNA obtained from a cortisol-producing adrenal tumor with a PRKACA p.Leu206Arg mutation.
2014-04-15 | E-GEOD-56016 | biostudies-arrayexpress
Project description:Background: Autonomous cortisol secretion (ACS), results from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, how other adrenal steroid metabolites affect bone status is unclear. Methods: ACS was diagnosed at serum cortisol after 1-mg dexamethasone suppression test (DST-cortisol) ≥ 1.8 g/dL. Using liquid chromatography-tandem mass spectrometry, we measured 21 plasma steroid metabolites in 73 patients with ACS and 85 with non-functioning adrenal tumors (NFAT). We also examined expression of steroidogenic enzymes and relevant steroid metabolites in some of CPA tissues. Results: In discriminant and principal component analysis, steroid profiles distinguished between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite; 11-deoxycorticosterone (11-DOC), with lower androgen metabolites; dehydroepiandrosterone-sulfate and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol was negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC was negatively correlated with lumbar spine-bone mineral density (r = -0.603), while androsterone-glucuronide was positively correlated with TBS (r = 0.681), which was supported by Bayesian kernel machine regression analysis. There were no such correlations in postmenopausal women and men. The CPA tissues showed increased levels of 11-DOC, with increased expression of CYP21A2, which is essential for 11-DOC synthesis. The adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, which is required for androgen synthesis. Conclusion: This study provides the first evidence that unbalanced production of adrenal steroid metabolites, which are derived from both adrenal tumors and non-tumor tissues, play a role in the pathogenesis of endogenous SIOP in premenopausal women with ACS.
2023-06-01 | E-MTAB-12895 | biostudies-arrayexpress
Project description:Maternal stress during late pregnancy can lead to intrauterine hyperthermia affecting fetal hypothalamic-pituitary-adrenal axis development and function. This study aimed to characterize the impact of in utero heat stress on the postnatal offspring's adrenal gland transcriptome.
2023-06-21 | GSE235160 | GEO
Project description:The study objective was to determine differentially expressed mRNA transcripts in perirenal adipose tissue from fetal sheep that underwent sham or adrenal demedullation prior to fetal growth restriction to determine the role of catecholamines on gene expression following placental insufficiency-induced intrauterine growth restriction.
2023-12-05 | GSE132734 | GEO
Project description:Programming effects of intrauterine hyperthermia on adrenal gland development
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Project description:Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 or 0.5 mg/kg/day cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n=8, maternal cortisol 1 mg/kg/day: n=6) or two-week-old lambs (control: n=7, maternal cortisol 0.5mg/kg/day: n=9). Transcriptomic modeling was used to identify pathways altered by maternal cortisol over-exposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition towards white fat at two weeks of age in EAT of control fetuses/lambs, and highlighted a role of immune responses, including complement-coagulation, and serotonin in this transition. Maternal cortisol (1mg/kg/day) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses, but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses. Conversely the transcriptomics in EAT of two-week-old lambs of ewes treated with a lower dose of cortisol (0.5mg/kg/day) suggested decreased metabolism of several substrates through both mitochondrial and cytosolic actions, and delayed maturation of EAT associated with a longer period of adipogenesis and angiogenesis.
2019-07-10 | GSE119254 | GEO
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, CushingM-bM-^@M-^Ys disease and chronic stress. 2 cohorts of singleton sheep fetuses at 129-131d gestation or 139-144d gestation (approximately term) were used. The first cohort received maternal cortisol infusion of 1mg/kg/day or vehicle for 10 days until approximately day 130 of gestation (n=6/group), the second cohort received the same dose of cortisol for approximately 25 days until near term (n=7, cortisol; n=7ewes, n=8 fetuses due to one set of twins, control)
2014-08-07 | E-GEOD-54237 | biostudies-arrayexpress
Project description:RNA Sequencing of Perirenal Adipose Tissue from Intrauterine Growth Restricted and Normally-Grown Near Term Sheep Fetuses with and without intact adrenal medulla.
| PRJNA548868 | ENA
Project description:Glucocorticoids act through the glucocorticoid receptor (GR), a ligand activated transcription factor, to modulate gene expression profiles in target cells and tissues. The principal physiological glucocorticoid in humans, cortisol, is released in a pulsatile fashion from the adrenal gland, which results in oscillations in blood concentrations, with a period of 1 - 2 hours. The biological consequence of fluctuating cortisol concentrations has not been explored. To identify the role of cortisol concentration oscillations for target cell response a flow-through cell culture system was developed. Transcription profiling was performed in the absence and presence of cortisol. Cells were exposed to constant cortisol levels of 100ng/ml or 200 ng/ml or oscillating cortisol concentrations.
2010-07-10 | E-MEXP-2447 | biostudies-arrayexpress