title: Antenatal maternal long-term hypoxia: acclimatization responses with altered gene expression in ovine fetal carotid arteries.
abstract: In humans and other species, long-term hypoxia (LTH) during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF), and other problems. To identify the signal transduction pathways and critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA) from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified mRNA from 38 genes upregulated >2 fold (P<0.05) and 9 genes downregulated >2-fold (P<0.05). The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF) binding protein 3, IGF type 2 receptor, transforming growth factor (TGF) Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. Most genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3' un translated region (UTR). Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L). We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may play a role in the acclimatization response to high-altitude associated LTH.
authors.affiliation: Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America ; Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Ravi
authors.initials: R
authors.lastname: Goyal
authors.affiliation: Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Van Wickle
authors.affiliation: Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Dipali
authors.initials: D
authors.lastname: Goyal
authors.affiliation: Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Matei
authors.affiliation: Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America ; Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012756:Sheep; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D053782:Transforming Growth Factor beta3; D056464:Histone Deacetylase 2