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Genomics of the ovine fetal brain ontogeny during the last stage of gestation

ABSTRACT: Normal development in the brain requires temporal changes in gene expression. A better understanding of the genomics of the fetal brain during late gestation can help to improve our understanding of the molecular events that enable the newborn to survive extra-uterine life. The purpose of the present study is to model changes and coherence of gene expression in cerebral cortex, brainstem, hippocampus, and hypothalamus throughout the second half of gestation. We used the sheep as an animal model to identify co-expressed genes in different regions of the ovine fetal brain, from mid-gestation (80 days) to one day of postnatal life. In the ewe, gestation length varies from 142 to 152 days, with an average of 147 days. Using a newly-available ovine array and weighted gene co-expression network analysis (WGCNA), we tested the hypothesis that the resulting products of genes expressed in a similar pattern through the last stage of gestation in different brain regions are functionally related and could play an important role in the normal fetal development.

ORGANISM(S): Ovis aries

PROVIDER: GSE50460 | GEO | 2014/06/30

SECONDARY ACCESSION(S): PRJNA217516

REPOSITORIES: GEO

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Genomics of the ovine fetal brain ontogeny during the last stage of gestation

Project description:Normal development in the brain requires temporal changes in gene expression. A better understanding of the genomics of the fetal brain during late gestation can help to improve our understanding of the molecular events that enable the newborn to survive extra-uterine life. The purpose of the present study is to model changes and coherence of gene expression in cerebral cortex, brainstem, hippocampus, and hypothalamus throughout the second half of gestation. We used the sheep as an animal model to identify co-expressed genes in different regions of the ovine fetal brain, from mid-gestation (80 days) to one day of postnatal life. In the ewe, gestation length varies from 142 to 152 days, with an average of 147 days. Using a newly-available ovine array and weighted gene co-expression network analysis (WGCNA), we tested the hypothesis that the resulting products of genes expressed in a similar pattern through the last stage of gestation in different brain regions are functionally related and could play an important role in the normal fetal development. Tissues from cortex, brainstem, hippocampus and hypothalamus were collected from non treated fetuses at 80 (80d, n=4), 96M-bM-^@M-^S100 (100d, n=4), 120 (120d, n=4), 130 (130d, n=4), and 142M-bM-^@M-^S144 (145d, n=4) days of gestation and on the first (1d, n=4) day after delivery. Each group included one set of twin fetuses. None of the ewes showed any signs of impending labor.

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Genomics of Estradiol-3-Sulfate Action in the Ovine Fetal Hypothalamus

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

Genomics of Estradiol-3-Sulfate Action in the Ovine Fetal Hypothalamus

2011-08-03 | GSE31184 | GEO

Genomics of the ovine heart ontogeny during the perinatal period

2015-07-30 | E-GEOD-66725 | biostudies-arrayexpress

Maternal Nurtritional Programming in the Ovine Mammary Gland

Project description:Developmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland.

2015-07-29 | GSE71424 | GEO

Maternal Nurtritional Programming in the Ovine Mammary Gland

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Effects of Triclosan exposition on fetal hypothalamic transcriptomics

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 Î¼g/day; n=4) iv. For indirect TCS exposure, TCS (100 Î¼g/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

Ketamine suppresses hypoxia-induced inflammatory responses in the late-gestation ovine fetal kidney cortex

Project description:Acute fetal hypoxia is a form of fetal stress that stimulates renal vasoconstriction and ischemia as a consequence of the physiological redistribution of combined ventricular output. We have demonstrated that hypoxia in late ovine gestation induces inflammation in the brain that is ameliorated by treatment with ketamine. We hypothesized that the fetal kidney would also respond to hypoxia with an increase in the expression of inflammatory genes, and that ketamine (an N-Methyl-D-aspartate receptor antagonist) would reduce or block this response. Enriched biological processes for the 427 upregulated genes were immune and inflammatory responses and for the 946 down-regulated genes were metabolic processes. Ketamine countered the effects of hypoxia on upregulated immune/inflammatory responses as well as the down-regulated metabolic responses. We conclude that our transcriptomics modeling predicts that hypoxia activates inflammatory pathways and reduces metabolism in the fetal kidney cortex, and ketamine blocks or ameliorates this response. The results suggest that ketamine may have therapeutic potential for protection from ischemic renal damage.

2016-09-01 | GSE66920 | GEO

A Systems Biology Understanding of Hypothalamic Inflammation Following Transient Hypoxia in the Late-Gestation Fetal Sheep

Project description:The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. However, little is known about the biochemical and molecular response of the fetal brain to transient hypoxia. The present study was designed to use transcriptomics and systems biology modeling to identify major biological responses of the fetal hypothalamus to transient hypoxia. We also investigated the effect of ketamine, an FDA approved anesthetic that has anti-inflammatory properties in various tissues. Chronically catheterized fetal sheep (122±5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2 ~50 %) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. Messenger RNA was isolated from fetal hypothalamus collected 24 hours after hypoxia, and was analyzed for gene expression using the Agilent 15.5k ovine microarray. Hypoxia increased expression of 280 and decreased expression of 357 genes. Genes increased by hypoxia were associated with immune responses, consistent with stimulation by lipopolysaccharide. Pretreatment of the fetuses with ketamine reduced immune/inflammation responses. Immunohistochemical analysis revealed that the number of microglia/macrophages in the anterior hypothalamus was increased by hypoxia and that the increase was blunted by ketamine. We conclude that transient hypoxia stimulates an inflammatory/immune response in the fetal hypothalamus and that transcriptomics/systems biology modeling is a useful and valid tool for investigation of biological function in the fetal sheep.

2017-07-31 | GSE82016 | GEO

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