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      The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility

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          Abstract

          Mitochondria play vital roles in oocyte functions and they are critical indicators of oocyte quality which is important for fertilization and development into viable offspring. Quality-compromised oocytes are correlated with infertility, developmental disorders, reduced blastocyst cell number and embryo loss in which mitochondrial dysfunctions play a significant role. Increasingly, women affected by metabolic disorders such as diabetes or obesity and oocyte aging are seeking treatment in IVF clinics to overcome the effects of adverse metabolic conditions on mitochondrial functions and new treatments have become available to restore oocyte quality. The past decade has seen enormous advances in potential therapies to restore oocyte quality and includes dietary components and transfer of mitochondria from cells with mitochondrial integrity into mitochondria-impaired oocytes. New technologies have opened up new possibilities for therapeutic advances which will increase the success rates for IVF of oocytes from women with compromised oocyte quality.

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          Most cited references129

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          Cell death: critical control points.

          Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
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            The mitochondrial permeability transition pore and its role in cell death.

            M Crompton (1999)
            This article reviews the involvement of the mitochondrial permeability transition pore in necrotic and apoptotic cell death. The pore is formed from a complex of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocase and cyclophilin-D (CyP-D) at contact sites between the mitochondrial outer and inner membranes. In vitro, under pseudopathological conditions of oxidative stress, relatively high Ca2+ and low ATP, the complex flickers into an open-pore state allowing free diffusion of low-Mr solutes across the inner membrane. These conditions correspond to those that unfold during tissue ischaemia and reperfusion, suggesting that pore opening may be an important factor in the pathogenesis of necrotic cell death following ischaemia/reperfusion. Evidence that the pore does open during ischaemia/reperfusion is discussed. There are also strong indications that the VDAC-adenine nucleotide translocase-CyP-D complex can recruit a number of other proteins, including Bax, and that the complex is utilized in some capacity during apoptosis. The apoptotic pathway is amplified by the release of apoptogenic proteins from the mitochondrial intermembrane space, including cytochrome c, apoptosis-inducing factor and some procaspases. Current evidence that the pore complex is involved in outer-membrane rupture and release of these proteins during programmed cell death is reviewed, along with indications that transient pore opening may provoke 'accidental' apoptosis.
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              Germline stem cells and follicular renewal in the postnatal mammalian ovary.

              A basic doctrine of reproductive biology is that most mammalian females lose the capacity for germ-cell renewal during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth. Here we show that juvenile and adult mouse ovaries possess mitotically active germ cells that, based on rates of oocyte degeneration (atresia) and clearance, are needed to continuously replenish the follicle pool. Consistent with this, treatment of prepubertal female mice with the mitotic germ-cell toxicant busulphan eliminates the primordial follicle reserve by early adulthood without inducing atresia. Furthermore, we demonstrate cells expressing the meiotic entry marker synaptonemal complex protein 3 in juvenile and adult mouse ovaries. Wild-type ovaries grafted into transgenic female mice with ubiquitous expression of green fluorescent protein (GFP) become infiltrated with GFP-positive germ cells that form follicles. Collectively, these data establish the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary.
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                Author and article information

                Contributors
                SchattenH@missouri.edu
                sunqy@ioz.ac.cn
                PratherR@missouri.edu
                Journal
                Reprod Biol Endocrinol
                Reprod. Biol. Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central (London )
                1477-7827
                24 November 2014
                24 November 2014
                2014
                : 12
                : 1
                : 111
                Affiliations
                [ ]Department of Veterinary Pathobiology, University of Missouri, Columbia, MO USA
                [ ]State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100080 China
                [ ]National Swine Resource and Research Center, University of Missouri, Columbia, 65211 USA
                [ ]Division of Animal Science, University of Missouri, Columbia, 65211 USA
                Article
                1300
                10.1186/1477-7827-12-111
                4297407
                25421171
                52c447d0-c157-442e-8b3b-e24ff4a9616c
                © Schatten et al.; licensee BioMed Central. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 July 2014
                : 4 September 2014
                Categories
                Review
                Custom metadata
                © The Author(s) 2014

                Human biology
                mitochondria,oocytes,embryos,embryo development,metabolism,in vitro fertilization,mitochondrial supplementation,infertility treatment

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