title: The p38 MAPK signalling pathway is required for glucose metabolism, lineage specification and embryo survival during mouse preimplantation development.
abstract: Preimplantation embryo development is an important and unique period and is strictly controlled. This period includes a series of critical events that are regulated by multiple signal-transduction pathways, all of which are crucial in the establishment of a viable pregnancy. The p38 mitogen-activated protein kinase (MAPK) signalling pathway is one of these pathways, and inhibition of its activity during preimplantation development has a deleterious effect. The molecular mechanisms underlying the deleterious effects of p38 MAPK suppression in early embryo development remain unknown. To investigate of the effect of p38 MAPK inhibition on late preimplantation stages in detail, we cultured 2-cell stage embryos in the presence of SB203580 for 48 h and analysed the 8-cell, morula, and blastocyst stages. We determined that prolonged inhibition of the p38 MAPK altered the expression levels of Glut1 and Glut4, decreased glucose uptake during the 8-cell to blastocyst transition, changed the expression levels of transcripts which will be important to lineage commitment, including Oct4/Pou5f1, Nanog, Sox2, and Gata6, and increased cell death in 8-16 cell stage embryos onwards. Strikingly, while the expression levels of Nanog, Gata6 and Oct4/Pou5f1 mRNAs were significantly decreased, Sox2 mRNA was increased in SB203580-treated blastocysts. Taken together, our results provide important insight into the biological processes controlled by the p38 MAPK pathway and its critical role during preimplantation development.
authors.affiliation: Department of Histology and Embryology, Akdeniz University, School of Medicine, Campus, 07070, Antalya, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Sozen
authors.affiliation: Department of Histology and Embryology, Akdeniz University, School of Medicine, Campus, 07070, Antalya, Turkey.
authors.forename: Saffet
authors.initials: S
authors.lastname: Ozturk
authors.affiliation: Department of Histology and Embryology, Istanbul Medipol University, School of Medicine, 34810, Beykoz, Istanbul, Turkey.
authors.forename: Aylin
authors.initials: A
authors.lastname: Yaba
authors.affiliation: Department of Histology and Embryology, Akdeniz University, School of Medicine, Campus, 07070, Antalya, Turkey. Electronic address: necdet08@yahoo.com.
authors.forename: Necdet
authors.initials: N
authors.lastname: Demir
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects; D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D005947:Glucose; C093642:SB 203580
keywords: GLUT; Lineage segregation; Mouse; P38 MAPK; Preimplantation