Unknown,Transcriptomics,Genomics,Proteomics

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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. 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.

ORGANISM(S): Ovis aries

SUBMITTER: Maria Rabaglino

PROVIDER: E-GEOD-50460 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Estradiol (E2) is a well-known modulator of fetal neuroendocrine activity, and has been proposed as a critical endocrine signal readying the fetus for birth and postnatal life. To investigate the modulatory role of E2 on fetal stress responsiveness and the response of the fetal brain to asphyxic stress, we subjected chronically catheterized fetal sheep to a transient (10 min) brachiocephalic occlusion or sham occlusion. Half of the fetuses received subcutaneous pellets that released E2 (5 days@~250 M-NM-<g/day, increasing plasma E2 from 62M-BM-16 to 102M-BM-112 pg/mL). Hypothalamic mRNA was analyzed using the Agilent 8x15k ovine array (019921), processed and annotated as previously reported by our laboratory. Analysis of the data by ANOVA revealed that E2 differentially regulated (DR) 561 genes, and BCO DR 894 genes compared to control and estradiol+BCO DR 1153 genes compared to BCO alone (all p<0.05). E2 upregulated epigenetic pathways and downregulated local steroid biosynthesis, but did not significantly involve genes known to directly respond to the estrogen receptor (ie., contain ERE sequences). BCO upregulated kinase pathways as well as genes associated with lymphocyte infiltration into the brain, and downregulated neuropeptide synthesis. E2 upregulated immune- and apopotosis- related pathways after BCO, and reduced kinase and epigenetic pathway responses to the BCO. We conclude that array results are consistent with the results of more limited hypotheses previously published from these experiments. Chronically catheterized fetal sheep; 4 groups: control (no treatment); estradiol treatment (250 ug/day x 5 days); brachiocephalic occlusion of fetal sheep (BCO, 10 min, no other treatment); BCO plus estradiol (combination of estradiol treatment and BCO). All fetuses had blood drawn from chronically implanted catheters at 0, 5, 10, and 30 min after start of BCO or sham-BCO period. Fetal sheep 124-128 days gestation (term=147 days) at the time of study. Fetuses euthanized and fetal hypothalami collected for gene array studies 1 hour after first blood sample drawn (and start of BCO or sham-BCO period).

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

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