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Expression patterns of mitochondrial OXPHOS components, mitofusin 1 and dynamin-related protein 1 are associated with human embryo fragmentation

Vesna Otasevic A D , Lela Surlan B , Milica Vucetic A , Ivan Tulic B , Biljana Buzadzic A , Ana Stancic A , Aleksandra Jankovic A , Ksenija Velickovic C , Igor Golic C , Milica Markelic C , Aleksandra Korac C and Bato Korac A D

A University of Belgrade, Department of Physiology, Institute for Biological Research ‘Sinisa Stankovic’, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
B The Clinic of Gynaecology and Obstetrics, Clinical Centre of Serbia, Koste Todorovica 26, 11000 Belgrade, Serbia.
C University of Belgrade, Faculty of Biology and Centre for Electron Microscopy, Studentski trg 16, 11000 Belgrade, Serbia.
D Corresponding authors. Email: vesna@ibiss.bg.ac.rs; koracb@ibiss.bg.ac.rs

Reproduction, Fertility and Development - http://dx.doi.org/10.1071/RD13415
Submitted: 5 December 2013  Accepted: 23 May 2014   Published online: 18 July 2014

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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.

Additional keywords: in vitro fertilisation, mitochondrial DNA, membrane potential.


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