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      Mammalian sperm nuclear organization: resiliencies and vulnerabilities

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          Abstract

          Sperm cells are remarkably complex and highly specialized compared to somatic cells. Their function is to deliver to the oocyte the paternal genomic blueprint along with a pool of proteins and RNAs so a new generation can begin. Reproductive success, including optimal embryonic development and healthy offspring, greatly depends on the integrity of the sperm chromatin structure. It is now well documented that DNA damage in sperm is linked to reproductive failures both in natural and assisted conception (Assisted Reproductive Technologies [ART]). This manuscript reviews recent important findings concerning - the unusual organization of mammalian sperm chromatin and its impact on reproductive success when modified. This review is focused on sperm chromatin damage and their impact on embryonic development and transgenerational inheritance.

          Résumé

          Les spermatozoïdes sont des cellules particulièrement complexes et très spécialisées comparées aux cellules somatiques. Leur rôle est de délivrer dans l’ovule le patrimoine génétique paternel ainsi qu’un lot de protéines et d’ARNs de façon à initier un nouvel individu. Le succès reproductif qui recouvre les aspects de développement embryonnaire harmonieux et de santé de la descendance repose en partie sur l’intégrité de la chromatine spermatique. Les dommages à l’ADN spermatique sont clairement associés aux échecs reproductifs que ce soit en reproduction naturelle et en procréation médicalement assistée (PMA). Cette revue présente les derniers développements concernant l’organisation très particulière de la chromatine spermatique et ses impacts sur le succès reproductif quand cette organisation est perturbée, en particulier sur le développement embryonnaire et les risques trangénérationnels.

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          Most cited references182

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          Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

          Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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            Histone core modifications regulating nucleosome structure and dynamics.

            Post-translational modifications of histones regulate all DNA-templated processes, including replication, transcription and repair. These modifications function as platforms for the recruitment of specific effector proteins, such as transcriptional regulators or chromatin remodellers. Recent data suggest that histone modifications also have a direct effect on nucleosomal architecture. Acetylation, methylation, phosphorylation and citrullination of the histone core may influence chromatin structure by affecting histone-histone and histone-DNA interactions, as well as the binding of histones to chaperones.
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              Histones: annotating chromatin.

              Chromatin is a highly regulated nucleoprotein complex through which genetic material is structured and maneuvered to elicit cellular processes, including transcription, cell division, differentiation, and DNA repair. In eukaryotes, the core of this structure is composed of nucleosomes, or repetitive histone octamer units typically enfolded by 147 base pairs of DNA. DNA is arranged and indexed through these nucleosomal structures to adjust local chromatin compaction and accessibility. Histones are subject to multiple covalent posttranslational modifications, some of which alter intrinsic chromatin properties, others of which present or hinder binding modules for non-histone, chromatin-modifying complexes. Although certain histone marks correlate with different biological outputs, we have yet to fully appreciate their effects on transcription and other cellular processes. Tremendous advancements over the past years have uncovered intriguing histone-related matters and raised important related questions. This review revisits past breakthroughs and discusses novel developments that pertain to histone posttranslational modifications and the affects they have on transcription and DNA packaging.
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                Author and article information

                Contributors
                (33)473407413 , joel.drevet@univ-bpclermont.fr
                Journal
                Basic Clin Androl
                Basic Clin Androl
                Basic and Clinical Andrology
                BioMed Central (London )
                2051-4190
                21 December 2016
                21 December 2016
                2016
                : 26
                : 17
                Affiliations
                [1 ]GReD “Genetics, Reproduction & Development” Laboratory, UMR CNRS 6293, INSERM U1103, Clermont Université, BP60026 - TSA60026, 63178 Aubière cedex, France
                [2 ]Centro Universitário Rio Preto, UNIRP, Rodovia Br153, Km 69, CEP15093-450 São José do Rio Preto, São Paulo Brazil
                [3 ]CellOxess LLC, 830 Bear Tavern Road, Ewing, NJ 08628 USA
                Article
                44
                10.1186/s12610-016-0044-5
                5175393
                6851e6ed-5196-4358-8c3a-9065395c989a
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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
                : 29 September 2016
                : 12 November 2016
                Funding
                Funded by: INSERM
                Funded by: CNRS
                Funded by: Clermont Université (FR)
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2016

                sperm dna damage,oxidative stress,infertility,developmental impacts,dommage à l’and spermatique,stress oxydant,infertilité,impacts developmentaux

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