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      Discovery of the Involvement in DNA Oxidative Damage of Human Sperm Nuclear Basic Proteins of Healthy Young Men Living in Polluted Areas

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          Abstract

          DNA oxidative damage is one of the main concerns being implicated in severe cell alterations, promoting different types of human disorders and diseases. For their characteristics, male gametes are the most sensitive cells to the accumulation of damaged DNA. We have recently reported the relevance of arginine residues in the Cu(II)-induced DNA breakage of sperm H1 histones. In this work, we have extended our previous findings investigating the involvement of human sperm nuclear basic proteins on DNA oxidative damage in healthy males presenting copper and chromium excess in their semen. We found in 84% of those males an altered protamines/histones ratio and a different DNA binding mode even for those presenting a canonical protamines/histones ratio. Furthermore, all the sperm nuclear basic proteins from these samples that resulted were involved in DNA oxidative damage, supporting the idea that these proteins could promote the Fenton reaction in DNA proximity by increasing the availability of these metals near the binding surface of DNA. In conclusion, our study reveals a new and unexpected behavior of human sperm nuclear basic proteins in oxidative DNA damage, providing new insights for understanding the mechanisms related to processes in which oxidative DNA damage is implicated.

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          Role of Oxidative Stress in Male Infertility: An Updated Review

          Current evidence links oxidative stress (OS) to male infertility, reduced sperm motility, sperm DNA damage and increased risk of recurrent abortions and genetic diseases. A review of PubMed, Medline, Google Scholar, and Cochrane review databases of published articles from years 2000–2018 was performed focusing on physiological and pathological consequences of reactive oxygen species (ROS), sperm DNA damage, OS tests, and the association between OS and male infertility, pregnancy and assisted reproductive techniques outcomes. Generation of ROS is essential for reproductive function, but OS is detrimental to fertility, pregnancy, and genetic status of the newborns. Further, there is a lack of consensus on selecting OS test, type, and duration of antioxidants treatment as well as on the target patients group. Developing advanced diagnostic and therapeutic options for OS is essential to improve fertility potential and limit genetic diseases transmitted to offspring.
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            Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

            Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.
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              Importance of chromium-DNA adducts in mutagenicity and toxicity of chromium(VI).

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                12 June 2020
                June 2020
                : 21
                : 12
                : 4198
                Affiliations
                [1 ]Department of Biology, University of Naples Federico II, 80126 Napoli, Italy; gennarole@ 123456outlook.com (G.L.); giov.dago@ 123456gmail.com (G.D.); elena.mele94@ 123456gmail.com (E.M.); carolina.cardito17@ 123456gmail.com (C.C.); rosa-expo@ 123456hotmail.it (R.E.)
                [2 ]CNR, Institute of Biochemistry and Cell Biology, via Pietro Castellino, 80131 Naples, Italy; cimmino.annalinda88@ 123456gmail.com
                [3 ]Department of Chemical Sciences, University of Naples Federico II, Via Cinthia, 21, 80126 Naples, Italy; antonella.giarra@ 123456unina.it (A.G.); marco.trifuoggi@ 123456unina.it (M.T.)
                [4 ]Seminology Unit Gentile Research Centre, 80054 Gragnano, Italy; salvatoreraimondo57@ 123456gmail.com
                [5 ]GEA—Gynecology Embryology Andrology—Reproductive Medicine Unit of Check Up Polydiagnostic Center, 84131 Salerno, Italy; tiziananotari7@ 123456gmail.com
                [6 ]Andrology Unit of the “S. Francesco d’Assisi” Hospital, Local Health Authority (ASL) Salerno, EcoFoodFertility Project Coordination Unit, 84020 Oliveto Citra, Italy
                Author notes
                [* ]Correspondence: ferdinando.febbraio@ 123456cnr.it (F.F.); l.montano@ 123456aslsalerno.it (L.M.); marina.piscopo@ 123456unina.it (M.P.); Tel.: +39-081-613-2611 (F.F.); +39-082-879-7111 (ext. 271) (L.M.); +39-081-679-081 (M.P.)
                [†]

                These authors contribute equally (co-first).

                [‡]

                These authors contribute equally (co-last).

                Author information
                https://orcid.org/0000-0003-1623-164X
                https://orcid.org/0000-0002-3653-9847
                https://orcid.org/0000-0001-5670-9439
                Article
                ijms-21-04198
                10.3390/ijms21124198
                7349829
                32545547
                4ff142da-e071-4667-8532-9c24fb5185b9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 May 2020
                : 10 June 2020
                Categories
                Article

                Molecular biology
                dna oxidative damage,protein–dna binding,human protamines,heavy metals,emsa,fluorescence

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