title: Fetal growth restriction caused by MIMT1 deletion alters brain transcriptome in cattle.
abstract: We examined levels of gene expression in the brains of bovine fetuses carrying a truncated MIMT1 allele, MIMT1(Del), shown to cause late abortion and stillbirth as a result of fetal growth restriction. MIMT1 is a non-protein coding gene that forms part of the imprinted PEG3 (paternally expressed gene 3) domain. Microarray analysis of brain cortex samples from mid-gestation MIMT1(Del/WT) bovine fetuses and wild-type siblings was performed to study the effect of fetal growth restriction on brain gene expression. Statistical analysis revealed 134 genes with increased mRNA levels and 22 with reduced levels in MIMT1(Del/WT) fetuses. Gene set enrichment analysis identified a relatively small number of significant functional clusters representing three major biological processes: response to oxidative stress, angiogenesis, and epithelial cell proliferation. Gene expression microarray analyses identified increased expression of VIPR2, HTRA1, S100A4 and MYH8 in fetuses carrying the deletion and decreased expression of DRD2, ADAM18, miR345, ZNF585A. ADAM18, DRD2 and S100A4 are known to be involved in prenatal brain development. ZNF585A, miR-345, VIPR2, HTRA1, and MYH8 are known to be involved in cell growth and differentiation, but any role in neural developmental has yet to be elucidated.
authors.affiliation: Department of Production Animal Medicine, University of Helsinki, Saarentaus, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Venhoranta
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauersachs
authors.forename: Juhani
authors.initials: J
authors.lastname: Taponen
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
authors.forename: Alexander
authors.initials: A
authors.lastname: Kind
authors.forename: Angelika
authors.initials: A
authors.lastname: Schnieke
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Flisikowski
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000473:pathology; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D000074289:High-Temperature Requirement A Serine Peptidase 1; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D046228:Microarray Analysis; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*
chemical_list: D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D051722:ADAM Proteins; D018995:Myosin Heavy Chains
keywords: Bos taurus; Fetal brain; Intrauterine growth restriction; Non-coding RNA; Oxidative stress