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      Oocyte ageing and epigenetics

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          Abstract

          It has become a current social trend for women to delay childbearing. However, the quality of oocytes from older females is compromised and the pregnancy rate of older women is lower. With the increased rate of delayed childbearing, it is becoming more and more crucial to understand the mechanisms underlying the compromised quality of oocytes from older women, including mitochondrial dysfunctions, aneuploidy and epigenetic changes. Establishing proper epigenetic modifications during oogenesis and early embryo development is an important aspect in reproduction. The reprogramming process may be influenced by external and internal factors that result in improper epigenetic changes in germ cells. Furthermore, germ cell epigenetic changes might be inherited by the next generations. In this review, we briefly summarise the effects of ageing on oocyte quality. We focus on discussing the relationship between ageing and epigenetic modifications, highlighting the epigenetic changes in oocytes from advanced-age females and in post-ovulatory aged oocytes as well as the possible underlying mechanisms.

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          Most cited references140

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          Fetal origins of coronary heart disease.

          The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.
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            Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.

            Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways. Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute-mediated catalysis in mammals.
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              Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality.

              Oocyte quality is a key limiting factor in female fertility, yet we have a poor understanding of what constitutes oocyte quality or the mechanisms governing it. The ovarian follicular microenvironment and maternal signals, mediated primarily through granulosa cells (GCs) and cumulus cells (CCs), are responsible for nurturing oocyte growth, development and the gradual acquisition of oocyte developmental competence. However, oocyte-GC/CC communication is bidirectional with the oocyte secreting potent growth factors that act locally to direct the differentiation and function of CCs. Two important oocyte-secreted factors (OSFs) are growth-differentiation factor 9 and bone morphogenetic protein 15, which activate signaling pathways in CCs to regulate key genes and cellular processes required for CC differentiation and for CCs to maintain their distinctive phenotype. Hence, oocytes appear to tightly control their neighboring somatic cells, directing them to perform functions required for appropriate development of the oocyte. This oocyte-CC regulatory loop and the capacity of oocytes to regulate their own microenvironment by OSFs may constitute important components of oocyte quality. In support of this notion, it has recently been demonstrated that supplementing oocyte in vitro maturation (IVM) media with exogenous OSFs improves oocyte developmental potential, as evidenced by enhanced pre- and post-implantation embryo development. This new perspective on oocyte-CC interactions is improving our knowledge of the processes regulating oocyte quality, which is likely to have a number of applications, including improving the efficiency of clinical IVM and thereby providing new options for the treatment of infertility.
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                Author and article information

                Journal
                Reproduction
                Reproduction
                REPRO
                Reproduction (Cambridge, England)
                Bioscientifica Ltd (Bristol )
                1470-1626
                1741-7899
                March 2015
                15 July 2014
                : 149
                : 3
                : R103-R114
                Affiliations
                [1]Reproductive Medicine Center, Henan Provincial People's Hospital , #7 Weiwu Road, Jinshui District, Zhengzhou, Henan Province, 450003, People's Republic of China
                [2]State Key Laboratory of Reproductive Biology , Institute of Zoology, Chinese Academy of Sciences , #1 Beichen West Road, Chaoyang District, Beijing, 100101, People's Republic of China
                [3]Reproductive Medicine Center, People's Hospital of Zhengzhou University , Zhengzhou, Henan Province, 450003, People's Republic of China
                [4]Department of Veterinary Pathobiology , University of Missouri , Columbia, Missouri, 65211, USA
                Author notes
                Correspondence should be addressed to C-L Zhang; zcl6086@ 123456gmail.com or to Q-Y Sun; Email: sunqy@ 123456ioz.ac.cn
                Article
                REP140242
                10.1530/REP-14-0242
                4397590
                25391845
                f1ec79f8-b4ef-47cf-a46e-8449769b030b
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 6 May 2014
                : 7 November 2014
                : 12 November 2014
                Categories
                Review

                Obstetrics & Gynecology
                Obstetrics & Gynecology

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