title: Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation.
abstract: Developmental dysfunction in embryos, such as a lethal level of fragmentation, is assumed to be mitochondrial in origin. This study investigated the molecular basis of mitochondrial impairment in embryo fragmentation. Transcription patterns of factors that determine mitochondrial functionality: (i) components of the oxidative phosphorylation (OXPHOS) - complex I, cytochrome b, complex IV and ATP synthase; (ii) mitochondrial membrane potential (MMP); (iii) mitochondrial DNA (mtDNA) content and (iv) proteins involved in mitochondrial dynamics, mitofusin 1 (Mfn1) and dynamin related protein 1 (Drp1) were examined in six-cells Day 3 non-fragmented (control), low-fragmented (LF) and high-fragmented (HF) human embryos. Gene expression of mitochondria-encoded components of complex I and IV, cytochrome b and mtDNA were increased in HF embryos compared with control and LF embryos. In LF embryos, expression of these molecules was decreased compared with control and HF embryos. Both classes of fragmented embryos had decreased MMP compared with control. LF embryos had increased gene expression of Mfn1 accompanied by decreased expression of Drp1, while HF embryos had decreased Mfn1 expression but increased Drp1 expression. The study revealed that each improper transcriptional (in)activation of mitochondria-encoded components of the OXPHOS during early in vitro embryo development is associated with a decrease in MMP and with embryo fragmentation. The results also showed the importance of mitochondrial dynamics in fragmentation, at least in the extent of this process.
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Otasevic
authors.affiliation: The Clinic of Gynaecology and Obstetrics, Clinical Centre of Serbia, Koste Todorovica 26, 11000 Belgrade, Serbia.
authors.forename: Lela
authors.initials: L
authors.lastname: Surlan
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Vucetic
authors.affiliation: The Clinic of Gynaecology and Obstetrics, Clinical Centre of Serbia, Koste Todorovica 26, 11000 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Tulic
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Buzadzic
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Stancic
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jankovic
authors.affiliation: University of Belgrade, Faculty of Biology and Centre for Electron Microscopy, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Velickovic
authors.affiliation: University of Belgrade, Faculty of Biology and Centre for Electron Microscopy, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Igor
authors.initials: I
authors.lastname: Golic
authors.affiliation: University of Belgrade, Faculty of Biology and Centre for Electron Microscopy, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Markelic
authors.affiliation: University of Belgrade, Faculty of Biology and Centre for Electron Microscopy, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korac
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research 'Sinisa Stankovic', Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Bato
authors.initials: B
authors.lastname: Korac
mesh_terms: D001755:Blastocyst / Q000378:metabolism* / Q000648:ultrastructure; D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D034281:Dynamins; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D046149:Embryo Culture Techniques; D005307:Fertilization in Vitro; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D004272:DNA, Mitochondrial; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D045303:Cytochromes b; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins; D042967:Electron Transport Complex I