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Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos.
Gürke, Jacqueline; Schindler, Maria; Pendzialek, S Mareike; Thieme, René; Grybel, Katarzyna J; Heller, Regine; Spengler, Katrin; Fleming, Tom P; Fischer, Bernd; Navarrete Santos, Anne.
Afiliação
  • Heller R; Department of Anatomy and Cell BiologyFaculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), GermanyInstitute of Molecular Cell BiologyCenter for Molecular Biomedicine, Hans-Knoell-Straße 2, D-07745 Jena, GermanyCentre for Biological SciencesSouthampton General Hospital, University of Southampton, Mailpoint 840, Tremona Road, Southampton SO16 6YD, UK.
  • Spengler K; Department of Anatomy and Cell BiologyFaculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), GermanyInstitute of Molecular Cell BiologyCenter for Molecular Biomedicine, Hans-Knoell-Straße 2, D-07745 Jena, GermanyCentre for Biological SciencesSouthampton General Hospital, University of Southampton, Mailpoint 840, Tremona Road, Southampton SO16 6YD, UK.
  • Fleming TP; Department of Anatomy and Cell BiologyFaculty of Medicine, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle (Saale), GermanyInstitute of Molecular Cell BiologyCenter for Molecular Biomedicine, Hans-Knoell-Straße 2, D-07745 Jena, GermanyCentre for Biological SciencesSouthampton General Hospital, University of Southampton, Mailpoint 840, Tremona Road, Southampton SO16 6YD, UK.
Reproduction ; 151(5): 465-76, 2016 May.
Article em En | MEDLINE | ID: mdl-26836250
ABSTRACT
The mammalian target of rapamycin complex 1 (mTORC1) is known to be a central cellular nutrient sensor and master regulator of protein metabolism; therefore, it is indispensable for normal embryonic development. We showed previously in a diabetic pregnancy that embryonic mTORC1 phosphorylation is increased in case of maternal hyperglycaemia and hypoinsulinaemia. Further, the preimplantation embryo is exposed to increased L-leucine levels during a diabetic pregnancy. To understand how mTOR signalling is regulated in preimplantation embryos, we examined consequences of L-leucine and glucose stimulation on mTORC1 signalling and downstream targets in in vitro cultured preimplantation rabbit blastocysts and in vivo. High levels of L-leucine and glucose lead to higher phosphorylation of mTORC1 and its downstream target ribosomal S6 kinase 1 (S6K1) in these embryos. Further, L-leucine supplementation resulted in higher embryonic expression of genes involved in cell cycle (cyclin D1; CCND1), translation initiation (eukaryotic translation initiation factor 4E; EIF4E), amino acid transport (large neutral amino acid transporter 2; Lat2 gene SLC7A8) and proliferation (proliferating cell nuclear antigen; PCNA) in a mTORC1-dependent manner. Phosphorylation of S6K1 and expression patterns of CCND1 and EIF4E were increased in embryos from diabetic rabbits, while the expression of proliferation marker PCNA was decreased. In these embryos, protein synthesis was increased and autophagic activity was decreased. We conclude that mammalian preimplantation embryos sense changes in nutrient supply via mTORC1 signalling. Therefore, mTORC1 may be a decisive mediator of metabolic programming in a diabetic pregnancy.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Blastocisto / Hiperamonemia / Complexos Multiproteicos / Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Serina-Treonina Quinases TOR / Hiperglicemia Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Blastocisto / Hiperamonemia / Complexos Multiproteicos / Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Serina-Treonina Quinases TOR / Hiperglicemia Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2016 Tipo de documento: Article