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      Should the current guidelines for the treatment of varicoceles in infertile men be re-evaluated?

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          Distinctive Chromatin in Human Sperm Packages Genes for Embryo Development

          Summary As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. However, we find the retained nucleosomes significantly enriched at loci of developmental importance including imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signaling factors. Importantly, histone modifications localize to particular developmental loci. H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain non-coding RNAs, and generally to paternally-expressed imprinted loci, but not paternally-repressed loci. Notably, H3K27me3 is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Finally, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.
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            Oxidative stress and male infertility--a clinical perspective.

            Oxidative stress occurs when the production of potentially destructive reactive oxygen species (ROS) exceeds the bodies own natural antioxidant defenses, resulting in cellular damage. Oxidative stress is a common pathology seen in approximately half of all infertile men. ROS, defined as including oxygen ions, free radicals and peroxides are generated by sperm and seminal leukocytes within semen and produce infertility by two key mechanisms. First, they damage the sperm membrane, decreasing sperm motility and its ability to fuse with the oocyte. Second, ROS can alter the sperm DNA, resulting in the passage of defective paternal DNA on to the conceptus. This review will provide an overview of oxidative biochemistry related to sperm health and will identify which men are most at risk of oxidative infertility. Finally, the review will outline methods available for diagnosing oxidative stress and the various treatments available.
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              The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy.

              Oxidative stress in the male germ line is thought to affect male fertility and impact upon normal embryonic development. Accordingly, fertility specialists are actively exploring the diagnosis of such stress in spermatozoa and evaluating the possible use of antioxidants to ameliorate this condition. In this review, evidence for the presence of oxidative stress in human spermatozoa, the origins of this phenomenon, its clinical significance in the aetiology of male infertility and recent advances in methods for its diagnosis and treatment are re-examined. Moreover, an extensive review of the results presented in published clinical studies has been conducted to evaluate the overall impact of oral antioxidants on measures of sperm oxidative stress and DNA damage. Administration of antioxidants to infertile men has been assessed in numerous clinical studies with at least 20 reports highlighting its effect on measures of oxidative stress in human spermatozoa. A qualitative but detailed review of the results revealed that 19 of the 20 studies conclusively showed a significant reduction relating to some measure of oxidative stress in these cells. Strong evidence also supports improved motility, particularly in asthenospermic patients. However, of these studies, only 10 reported pregnancy-related outcomes, with 6 reporting positive associations. Adequately powered, placebo-controlled comprehensive clinical trials are now required to establish a clear role for antioxidants in the prevention of oxidative stress in the male germ line, such that the clinical utility of this form of therapy becomes established once and for all.
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                Author and article information

                Journal
                Human Fertility
                Human Fertility
                Informa UK Limited
                1464-7273
                1742-8149
                March 15 2021
                March 23 2019
                March 15 2021
                : 24
                : 2
                : 78-92
                Affiliations
                [1 ]The Urology Centre, Guy’s Hospital, London, UK
                [2 ]Department of Biosciences, University of Kent, Canterbury, UK
                [3 ]Department of Men’s Health and Andrology, Imperial College Healthcare, London, UK
                [4 ]Newcastle Fertility Centre, The Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK
                Article
                10.1080/14647273.2019.1582807
                81a39191-7155-4a2c-853b-7a70ee190938
                © 2021
                History

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