Genomics of the ovine heart ontogeny during the perinatal period
Ontology highlight
ABSTRACT:
ORGANISM(S): Ovis aries
SUBMITTER: Maria Rabaglino
PROVIDER: E-GEOD-66725 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The period of development from the last two weeks of gestation through the first two weeks of life spans a period of great functional and metabolic challenge to the fetal and neonatal lamb heart. Important changes in gene expression occur to meet these challenges. On this study, septa from sheep hearts at 130 days gestation (n=6), term (n=8, gestational lenght is around 145 days) and 14-days-old lambs (n=8) were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. Weighted gene co-expression network analysis (WGCNA) determined five major patterns of co-expressed and functionally related genes during this critical period of cardiac transition.
2015-07-30 | GSE66725 | 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:The late-gestation fetal lung has relatively high levels of expression of the mineralocorticoid receptor (MR) as well as the glucocorticoid receptor (GR), suggesting that endogenous corticosteroids may act in the lung through binding at MR as well as GR. This study was designed to determine the effects of physiologically relevant increases in steroids on MR and GR in the late-gestation lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both agonists were infused intravenously for 48 hours in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC and Na,K ATPase, and elastin and collagen content were determined at the end of the infusions. We found that aldosterone significantly reduced the initial airway pressures measured in situ during inflation. This effect did not occur with betamethasone alone or in combination with aldosterone. Conversely, betamethasone, but not aldosterone, significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs. Aldosterone altered novel gene pathways in the fetal lung, suggesting effects on lung compliance via genes which influence immune pathways and lung stiffness. The results are consistent with corticosteroid-induced fluid reabsorption at birth through GR rather than MR, but suggest that MR contributes effects facilitating lung inflation with the first breaths via nonclassical mechanisms. 4 sets of twin sheep fetuses at approximately 130d gestation (term is 147d) were used. One twin was infused with 0.2 mg aldosterone for 48 h, the other received vehicle.
2014-08-07 | E-GEOD-53048 | biostudies-arrayexpress
Project description:Triclosan (TCS), an antibacterial compound commonly added to personal care products, could be an endocrine disruptor at low doses. Although TCS has been shown to alter fetal physiology, its effects in the developing fetal brain are unknown. The objective of this study was to use transcriptomics and systems analysis to determine significantly altered biological processes in the late gestation ovine fetal hypothalamus after direct or indirect exposure to low doses of TCS. We found that short-term infusion of TCS induces vigorous changes in the fetal hypothalamic transcriptomics, which are mainly related to food intake pathways and metabolism. For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n=4) or TCS (250 μg/day; n=4) iv. For indirect TCS exposure, TCS (100 μg/kg/day; n=3) or vehicle (n=3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured using Agilent 15k ovine microarrays.
2016-02-29 | E-GEOD-69275 | biostudies-arrayexpress
Project description:Purpose: ATAC-seq was performed on preterm lambs that were ventilated by invasive mechanical ventilation or noninvasive respiratory support utilizing a mask and compared to gestation-age-matched preterm lambs that were not ventilated and naturally delivered term lambs. Methods: Lung chromatin access profiles were generated for: 1) Unventilated preterm lamb, 2) preterm lambs delivered at gd131 and intubated and mechanically ventilated for 3 days, 3) preterm lambs delivered at gd131 and not intubated and resuscitated by placing a face mask over the nose and mouth and controlling O2 delivery via a computer-controlled electronic blower device, 4) unventilated naturally delivered full-term lambs. Results: Using an optimized data analysis workflow, we mapped between 76 and 96 million sequence reads per sample to the sheep genome Conclusions: Our study represents the first detailed analysis of ventilated preterm lung chromatin access, with biologic replicates, generated by ATAC-seq
2021-06-30 | GSE163807 | GEO
Project description:This study aimed to use a lamb model of preterm birth to investigate the impact of different tidal volume strategies, applied during positive pressure ventilation, on lung injury development. Preterm lambs were ventilated for a total of 15 minutes, followed by a 30 minute ‘rest’ period where lambs were supported via the intact placenta. A group of lambs was also euthanised at birth to act as an unventilated control group. At post-mortem lung tissue was sampled for proteomic analysis. Lung tissue samples were analysed by mass spectrometry-based proteomics using a TMT-11plex labelling approach, followed by nano-liquid chromatography coupled to an Q Exactive HF-X benchtop Orbitrap mass spectrometer in a data-dependent acquisition mode.
2023-10-09 | PXD041917 | Pride
Project description:In the fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40-100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E2S) action in the fetal brain. The hypothesis was that E2S stimulates genes involved in the neuroendocrine pathways in the hypothalamus that direct or facilitate fetal development at the end of gestation. Four sets of chronically-catheterized ovine twin fetuses were studied (gestational age: 120-127 days gestation) with one infused with E2S intracerebroventricularly (1 mg/day) and the other remained untreated (control). After euthanasia, mRNA samples were extracted from the 8 hypothalami, corresponding to the four treatment and four control fetuses. Microarray analysis was performed following the Agilent protocol for 1-color 8x15 microarrays, designed for Ovis aries. A total of 4 sets of chronically-catheterized ovine twin fetuses were studied with one infused with estradiol-3-sulfate intracerebroventricularly (1 mg/day) for 7-12 days, using an osmotic mini-pump implanted in the fetus, and the other served as an untreated control. The gestational age at the time of surgery was 120-127 days of gestation. Twin fetuses were randomly assigned to the two groups at the time of surgery. After 7-12 days of infusion, twin fetuses of known gestational age (130 to 134 days) were euthanized and mRNA samples were extracted from the 8 hypothalami, corresponding to the four treatment and four control fetuses.
2011-08-02 | E-GEOD-31184 | biostudies-arrayexpress
Project description:Expression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) The fetal to neonatal developmental transition corresponds with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels occurring during the major developmental transition. We tested the hypothesis that this period is associated with changes in the transcription of skeletal muscle genes, particularly genes involved in oxidative metabolism. Using an ovine model, transcriptional profiling was performed on longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) as well as two postnatal time points, one within 3 days after birth and a second at 12 weeks of age. The developmental time course was dominated by large changes in the expression of 2471 genes during the period from late fetal development (120 d fetal development) to birth (within 1-3 days of birth). Analysis of the functions of the genes that were uniquely up-regulated in this period showed strong enrichment for oxidative metabolism and the TCA cycle indicating enhanced mitochondrial activity. Indeed, histological examination of tissues from these developmental time points directly demonstrated a marked increase in mitochondrial activity between the late fetal and early post-natal samples. The genes that were down-regulated in this period suggested de-emphasis of an array of biological functions including Wnt signaling, cell adhesion and differentiation. There were also changes in the expression of genes prior to this late fetal â postnatal transition and between the two postnatal time points that involved a variety of biological functions. It is concluded that there is substantial and coordinated changes in the transcription of a large number of genes in skeletal muscle which underpin the adaption of muscle to the new physiological demands in the postnatal environment. Microarrays were used for transcription profiling of skeletal muscle samples taken from fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) Sheep used in this experiment were bred from a research flock of Dorset/Suffolk/Rambouillet cross-bred sheep raised at Utah State University and cared for and euthanased for sample collection in accordance with the animal ethics guidelines of Utah State University (Utah, USA). Longissimus dorsi (LD) skeletal muscle samples were taken from fetal lambs at 80, 100 and 120 days of gestation, new born lambs within 1 to 3 days of birth (i.e. 150 days of development) and young lambs at 12 weeks of age (230 days of development). Three individuals were sampled at each developmental time
2010-06-08 | E-GEOD-20112 | biostudies-arrayexpress
Project description:Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106-107 days), control late pre-term (127 days), and experimental lambs who were born pre-term and supported on EXTEND until late pre-term age (125-128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs. Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.
2024-11-21 | GSE275228 | GEO
Project description:Expression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d) The fetal to neonatal developmental transition corresponds with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels occurring during the major developmental transition. We tested the hypothesis that this period is associated with changes in the transcription of skeletal muscle genes, particularly genes involved in oxidative metabolism. Using an ovine model, transcriptional profiling was performed on longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) as well as two postnatal time points, one within 3 days after birth and a second at 12 weeks of age. The developmental time course was dominated by large changes in the expression of 2471 genes during the period from late fetal development (120 d fetal development) to birth (within 1-3 days of birth). Analysis of the functions of the genes that were uniquely up-regulated in this period showed strong enrichment for oxidative metabolism and the TCA cycle indicating enhanced mitochondrial activity. Indeed, histological examination of tissues from these developmental time points directly demonstrated a marked increase in mitochondrial activity between the late fetal and early post-natal samples. The genes that were down-regulated in this period suggested de-emphasis of an array of biological functions including Wnt signaling, cell adhesion and differentiation. There were also changes in the expression of genes prior to this late fetal – postnatal transition and between the two postnatal time points that involved a variety of biological functions. It is concluded that there is substantial and coordinated changes in the transcription of a large number of genes in skeletal muscle which underpin the adaption of muscle to the new physiological demands in the postnatal environment. Microarrays were used for transcription profiling of skeletal muscle samples taken from fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d)
2010-06-01 | GSE20112 | GEO