Advances in Experimental Medicine and Biology
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1 Advances in Experimental Medicine and Biology Editorial Board: IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA RODOLFO PAOLETTI, University of Milan, Milan, Italy For further volumes:
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3 Elisabetta Baldi Monica Muratori Editors Genetic Damage in Human Spermatozoa
4 Editors Elisabetta Baldi Department of Experimental and Clinical Biomedical Sciences University of Florence Florence, Italy Monica Muratori Department of Experimental and Clinical Biomedical Sciences University of Florence Florence, Italy ISSN ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media New York 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
5 To our mentor, professor Mario Serio
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7 Preface The goal of male gametes is to deliver a fully intact and functioning paternal genome to the oocyte. To fulfill this aim, the process of chromatin maturation during spermiogenesis must be correctly completed to guarantee DNA protection during the long journey to reach the oocyte and to properly decondense and form the male pronucleus after fertilization. In this scenario, any condition or agent that can interfere with this complex process represents a threat to safe embryo formation and development and to the birth of healthy offspring. Concerns about these risks acquire particular relevance in the present era of assisted reproduction techniques that bypass several, if not all (as in the case of intracytoplasmic sperm injection), natural barriers designed to prevent fertilization by sperm that has significant genetic damage. This book presents an overview of the various types of damage that may affect the genetic material of the male gamete. Genetic damage in spermatozoa can occur during spermatogenesis or during transit in both male and female genital tracts, or it may be due to aging, environmental or iatrogenic conditions, or to the protocols used in cryopreserving and selecting spermatozoa in assisted reproduction techniques. Two chapters of the book are dedicated to the hot topic of sperm epigenome and epigenetic damage that may generate important and unexpected transgenerational effects. In addition, since so far the only proposed therapy to prevent sperm DNA damage is the administration of antioxidant compounds, the last chapter of the book is dedicated to this controversial issue. We wish to thank all the authors for their invaluable contributions to the book. They are all expert scientists in the field, and we appreciate their willingness to offer their knowledge in this important branch of reproductive medicine. We hope that this book will help researchers in the field of reproduction and serve as a reference for medical and technical staff working in laboratories investigating assisted reproduction techniques. Florence, Italy E. Baldi M. Muratori vii
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9 Contents 1 Structure of Chromatin in Spermatozoa... 1 Lars Björndahl and Ulrik Kvist 2 Genomic Changes in Spermatozoa of the Aging Male Chiara Chianese, Sara Brilli, and Csilla Krausz 3 Chromosomal Aberrations and Aneuploidies of Spermatozoa Paola Piomboni, Anita Stendardi, and Laura Gambera 4 The Sperm Epigenome: Implications for the Embryo John R. Gannon, Benjamin R. Emery, Timothy G. Jenkins, and Douglas T. Carrell 5 Environmental Epigenetics and Effects on Male Fertility Carlos Guerrero-Bosagna and Michael K. Skinner 6 Protamine Alterations in Human Spermatozoa Meritxell Jodar and Rafael Oliva 7 Sperm DNA Fragmentation and Base Oxidation Sheena E.M. Lewis 8 Iatrogenic Genetic Damage of Spermatozoa Cristian O Flaherty 9 Sperm Cryopreservation: Effects on Chromatin Structure Donatella Paoli, Francesco Lombardo, Andrea Lenzi, and Loredana Gandini ix
10 x Contents 10 Sperm Selection: Effect on Sperm DNA Quality Lodovico Parmegiani, Graçiela Estela Cognigni, and Marco Filicori 11 Effect of Antioxidants on Sperm Genetic Damage Yves Menezo, Don Evenson, Marc Cohen, and Brian Dale Erratum... Index E1
11 Contributors Lars Björndahl Centre for Andrology and Sexual Medicine, Clinic for Endocrinology, Karolinska University Hospital, Huddinge, Stockholm, Sweden Centre for Andrology and Sexual Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Sweden Sara Brilli Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy Douglas T. Carrell Division of Urology, Department of Surgery, Department of Obstetrics and Gynecology, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA Chiara Chianese Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy Graçiela Estela Cognigni GynePro Medical Centers, Reproductive Medicine Unit, Bologna, Italy Marc Cohen Procrelys, avenue Rockefeller, Lyon, France Brian Dale London Fertility Associates, London, UK Centre for Assisted Fertilization, Naples, Italy Benjamin R. Emery Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA Don Evenson South Dakota State University, Brookings, SD, USA Marco Filicori GynePro Medical Centers, Reproductive Medicine Unit, Bologna, Italy Laura Gambera Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy Center for Diagnosis and Treatment of Couple Sterility, S. Maria alle Scotte Hospital, Siena, Italy xi
12 xii Contributors Loredana Gandini Department of Experimental Medicine, University Laboratory of Seminology Sperm Bank, University of Rome La Sapienza, Rome, Italy John R. Gannon Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA Carlos Guerrero-Bosagna Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, USA Timothy G. Jenkins Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA Meritxell Jodar Human Genetics Research Group, IDIBAPS, University of Barcelona, Barcelona, Spain Csilla Krausz Andrology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy Ulrik Kvist Centre for Andrology and Sexual Medicine, Clinic for Endocrinology, Karolinska University Hospital, Huddinge, Stockholm, Sweden Centre for Andrology and Sexual Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden Andrea Lenzi Department of Experimental Medicine, University Laboratory of Seminology Sperm Bank, University of Rome La Sapienza, Rome, Italy Sheena E.M. Lewis Centre for Public Health, Queen s University Belfast, Belfast, Northern Ireland, UK Institute of Pathology, Belfast, Northern Ireland, UK Francesco Lombardo Department of Experimental Medicine, University Laboratory of Seminology Sperm Bank, University of Rome La Sapienza, Rome, Italy Yves Menezo London Fertility Associates, London, UK Laboratoire CLEMENT, Paris, France Cristian O Flaherty Division of Urology, Department of Surgery, McGill University and the Research Institute-McGill University Health Centre, Montréal, Québec, Canada Rafael Oliva Biochemistry and Molecular Genetics Service, Clinic Hospital, Villarroel, Barcelona, Spain Faculty of Medicine, University of Barcelona, and Institut d Investigacions Biomèdiques, Spain Donatella Paoli Department of Experimental Medicine, University Laboratory of Seminology Sperm Bank, University of Rome La Sapienza, Rome, Italy
13 Contributors xiii Lodovico Parmegiani GynePro Medical Centers, Reproductive Medicine Unit, Bologna, Italy Paola Piomboni Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy Center for Diagnosis and Treatment of Couple Sterility, S. Maria alle Scotte Hospital, Siena, Italy Michael K. Skinner Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, USA Anita Stendardi Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
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