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      Epigenetic Aberration of FMR1 Gene in Infertile Women with Diminished Ovarian Reserve

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          Abstract

          Objective

          The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women.

          Materials and Methods

          In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples.

          Results

          Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups.

          Conclusion

          Our data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

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          Most cited references31

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          Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.

          CpG methylation in vertebrates correlates with alterations in chromatin structure and gene silencing. Differences in DNA-methylation status are associated with imprinting phenomena and carcinogenesis. In Xenopus laevis oocytes, DNA methylation dominantly silences transcription through the assembly of a repressive nucleosomal array. Methylated DNA assembled into chromatin binds the transcriptional repressor MeCP2 which cofractionates with Sin3 and histone deacetylase. Silencing conferred by MeCP2 and methylated DNA can be relieved by inhibition of histone deacetylase, facilitating the remodelling of chromatin and transcriptional activation. These results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.
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            Ovarian aging: mechanisms and clinical consequences.

            Menopause is the final step in the process referred to as ovarian ageing. The age related decrease in follicle numbers dictates the onset of cycle irregularity and the final cessation of menses. The parallel decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility. Endocrine changes mainly relate to the decline in the negative feedback from ovarian factors at the hypothalamo-pituitary unit. The declining cohort of antral follicles with age first results in gradually elevated FSH levels, followed by subsequent stages of overt cycle irregularity. The gradual decline in the size of the antral follicle cohort is best represented by decreasing levels of anti-Mullerian hormone. The variability of ovarian ageing among women is evident from the large variation in age at menopause. The identification of women who have severely decreased ovarian reserve for their age is clinically relevant. Ovarian reserve tests have appeared to be fairly accurate in predicting response to ovarian stimulation in the assisted reproductive technology (ART) setting. The capacity to predict the chances for spontaneous pregnancy or pregnancy after ART appears very limited. As menopause and the preceding decline in oocyte quality seem to have a fixed time interval, tests that predict the age at menopause may be useful to assess individual reproductive lifespan. Especially genetic studies, both addressing candidate gene and genome wide association, have identified several interesting loci of small genetic variation that may determine fetal follicle pool development and subsequent wastage of his pool over time. Improved knowledge of the ovarian ageing mechanisms may ultimately provide tools for prediction of menopause and manipulation of the early steps of folliculogenesis for the purpose of contraception and fertility lifespan extension.
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              • Abstract: found
              • Article: not found

              Heterochromatin and epigenetic control of gene expression.

              Eukaryotic DNA is organized into structurally distinct domains that regulate gene expression and chromosome behavior. Epigenetically heritable domains of heterochromatin control the structure and expression of large chromosome domains and are required for proper chromosome segregation. Recent studies have identified many of the enzymes and structural proteins that work together to assemble heterochromatin. The assembly process appears to occur in a stepwise manner involving sequential rounds of histone modification by silencing complexes that spread along the chromatin fiber by self-oligomerization, as well as by association with specifically modified histone amino-terminal tails. Finally, an unexpected role for noncoding RNAs and RNA interference in the formation of epigenetic chromatin domains has been uncovered.
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                Author and article information

                Journal
                Cell J
                Cell J
                Royan Institute
                Cell Journal (Yakhteh)
                Royan Institute
                2228-5806
                2228-5814
                Spring 2018
                01 January 2018
                : 20
                : 1
                : 78-83
                Affiliations
                [1 ] Department of Biology, Faculty of Science, Science and Research Branch Islamic Azad University, Tehran, Iran
                [2 ]Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
                [3 ]Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
                [4 ]Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
                Author notes
                [*Corresponding Address: ]P.O. BOX: 16635-148Department of GeneticsReproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine ACECRTehranIran Emails: m.shahhoseini@ 123456royaninstitute.org , anahitamohseni@ 123456royaninstitute.org
                Article
                Cell-J-20-78
                10.22074/cellj.2018.4398
                5759683
                29308622
                d221e3b0-b9ea-4127-b436-fb45469336b3
                Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 June 2016
                : 15 January 2017
                Categories
                Original Article
                Genetics
                Gynecology and Female Infertility
                Custom metadata
                Eslami H, Eslami A, Favaedi R, Asadpour U, Zari Moradi Sh, Eftekhari-Yazdi P, Madani T, Shahhoseini M, Mohseni Meybodi A. Epigenetic aberration of FMR1 gene in infertile women with diminished ovarian reserve. Cell J. 2018; 20(1): 78-83. doi: 10.22074/cellj.2018.4398.

                epigenetic,fmr1 gene,histone modification,ovarian reserve cell journal(yakhteh),vol 20,no 1,apr-jun (spring) 2018,pages: 78-83

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