Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma

Frias, Sara; Van Hummelen, Paul; Meistrich, Marvin L.; Wyrobek, Andrew J.; Drevet, ed., Joël R.

doi:10.1371/journal.pone.0242218

Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma

Journal Article · Mon Dec 28 00:00:00 EST 2020 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0242218· OSTI ID:1749970

; Van Hummelen, Paul; Meistrich, Marvin L.; ; Drevet, ed., Joël R.

Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual’s burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; W-7405-ENG-48

OSTI ID:: 1749970

Alternate ID(s):: OSTI ID: 1798739

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 12 Vol. 15; ISSN 1932-6203

Publisher:: Public Library of Science (PLoS)Copyright Statement

Country of Publication:: United States

Language:: English

References (52)

Epididymal sperm aneuploidies in three strains of rats detected by multicolor fluorescence in situ hybridization Lowe, X. R.; de Stoppelaar, J. M.; Bishop, J. Environmental and Molecular Mutagenesis, Vol. 31, Issue 2 https://doi.org/10.1002/(SICI)1098-2280(1998)31:2<125::AID-EM4>3.0.CO;2-L	journal	January 1998
Numerical and structural chromosomal abnormalities detected in human sperm with a combination of multicolor FISH assays Baumgartner, A.; Van Hummelen, P.; Lowe, X. R. Environmental and Molecular Mutagenesis, Vol. 33, Issue 1 https://doi.org/10.1002/(SICI)1098-2280(1999)33:1<49::AID-EM6>3.0.CO;2-F	journal	January 1999
Temporary effects of AMSA (4′-(9-acridinylamino) methanesulfon-m-anisidide) chemotherapy on spermatogenesis Da Cunha, Miguel F.; Meistrich, Marvin L.; Haq, Mohamed M. Cancer, Vol. 49, Issue 12 https://doi.org/10.1002/1097-0142(19820615)49:12<2459::AID-CNCR2820491207>3.0.CO;2-Q	journal	June 1982
Detection of sex chromosomal aneuploidies X-X, Y-Y, and X-Y in human sperm using two-chromosome fluorescence in situ hybridization Wyrobek, Andrew J.; Robbins, Wendie A.; Mehraein, Yasmin American Journal of Medical Genetics, Vol. 53, Issue 1 https://doi.org/10.1002/ajmg.1320530102	journal	October 1994
Mechanisms and consequences of paternally-transmitted chromosomal abnormalities Marchetti, Francesco; Wyrobek, Andrew J. Birth Defects Research Part C: Embryo Today: Reviews, Vol. 75, Issue 2 https://doi.org/10.1002/bdrc.20040	journal	January 2005
Assessing human germ-cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell Wyrobek, Andrew J.; Mulvihill, John J.; Wassom, John S. Environmental and Molecular Mutagenesis, Vol. 48, Issue 2 https://doi.org/10.1002/em.20284	journal	January 2007
Persistent genomic instability in peripheral blood lymphocytes from hodgkin lymphoma survivors Salas, C.; Niembro, A.; Lozano, V. Environmental and Molecular Mutagenesis, Vol. 53, Issue 4 https://doi.org/10.1002/em.21691	journal	March 2012
Genomic chaos in peripheral blood lymphocytes of Hodgkin's lymphoma patients one year after ABVD chemotherapy/radiotherapy: Genomic Chaos in Peripheral Blood Lymphocytes Ramos, Sandra; Navarrete-Meneses, Pilar; Molina, Bertha Environmental and Molecular Mutagenesis, Vol. 59, Issue 8 https://doi.org/10.1002/em.22216	journal	September 2018
Mitoxantrone, More than Just Another Topoisomerase II Poison: MITOXANTRONE, MORE THAN JUST A TOPOISOMERASE II POISON Evison, Benny J.; Sleebs, Brad E.; Watson, Keith G. Medicinal Research Reviews, Vol. 36, Issue 2 https://doi.org/10.1002/med.21364	journal	August 2015
Fluorescence In situ hybridization to Y chromosomes in decondensed human sperm nuclei Wyrobek, Andrew J.; Alhborn, Thomas; Balhorn, Rod Molecular Reproduction and Development, Vol. 27, Issue 3 https://doi.org/10.1002/mrd.1080270304	journal	November 1990
Aneuploidy in late-step spermatids of mice detected by two-chromosome fluorescencein situ hybridization Wyrobek, A.; Lowe, X.; Pinkel, D. Molecular Reproduction and Development, Vol. 40, Issue 2 https://doi.org/10.1002/mrd.1080400216	journal	February 1995
Chromosomal damage in sperm of patients surviving Hodgkin's disease following MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) therapy with and without radiotherapy Brandriff, B. F.; Meistrich, M. L.; Gordon, L. A. Human Genetics, Vol. 93, Issue 3 https://doi.org/10.1007/BF00212026	journal	March 1994
Chromosomal abnormalities in human sperm: Comparisons among four healthy men Brandriff, B.; Gordon, L.; Ashworth, L. Human Genetics, Vol. 66, Issue 2-3 https://doi.org/10.1007/BF00286600	journal	April 1984
Chromosomes of human sperm: Variability among normal individuals Brandriff, B.; Gordon, L.; Ashworth, L. Human Genetics, Vol. 70, Issue 1 https://doi.org/10.1007/BF00389451	journal	May 1985
Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions Neuhäusler, Lisa; Summerer, Anna; Cooper, David N. Human Genetics, Vol. 137, Issue 5 https://doi.org/10.1007/s00439-018-1888-x	journal	May 2018
Simultaneous detection of structural and numerical chromosome abnormalities in sperm of healthy men by multicolor fluorescence in situ hybridization Hummelen, P. Van; Lowe, X. R.; Wyrobek, Andrew J. Human Genetics, Vol. 98, Issue 5 https://doi.org/10.1007/s004390050268	journal	September 1996
Response of mouse spermatogonial stem cells to X-ray induction of heritable reciprocal translocations Generoso, W. M.; Cain, K. T.; Cacheiro, N. L. A. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 126, Issue 2 https://doi.org/10.1016/0027-5107(84)90060-5	journal	April 1984
Lack of correlation between mutagen-induced chromosomal univalency and aneuploidy in mouse spermatocytes Liang, Jan C.; Sherron, David A.; Johnston, Dennis Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 163, Issue 3 https://doi.org/10.1016/0027-5107(86)90027-8	journal	December 1986
Detection of aneuploidy in human and rodent sperm using FISH and applications of sperm assays of genetic damage in heritable risk evaluation Wyrobek, A. J.; Adler, I. -D. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 352, Issue 1-2 https://doi.org/10.1016/0027-5107(95)00249-9	journal	June 1996
Mutagenicity of anticancer drugs in mammalian germ cells Witt, Kristine L.; Bishop, Jack B. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 355, Issue 1-2 https://doi.org/10.1016/0027-5107(96)00029-2	journal	August 1996
Detection of vincristine-induced hyperploidy in meiotic II metaphases of male Chinese hamsters Sheu, C. W.; Lee, J. K.; Arras, C. A. Mutation Research/Genetic Toxicology, Vol. 280, Issue 3 https://doi.org/10.1016/0165-1218(92)90047-4	journal	September 1992
Analysis of chromosomal abnormalities in human sperm after chemotherapy by karyotyping and fluorescence in situ hybridization (FISH) Martin, Renée H.; Rademaker, Alfred W.; Leonard, Norma Jean Cancer Genetics and Cytogenetics, Vol. 80, Issue 1 https://doi.org/10.1016/0165-4608(94)00162-5	journal	March 1995
A Stable Isotope-Mass Spectrometric Method for Measuring Human Spermatogenesis Kinetics In Vivo Misell, L. M.; Holochwost, D.; Boban, D. Journal of Urology, Vol. 175, Issue 1 https://doi.org/10.1016/S0022-5347(05)00053-4	journal	January 2006
Spontaneous rates of sex chromosomal aneuploidies in sperm and offspring of mice: a validation of the detection of aneuploid sperm by fluorescence in situ hybridization Adler, I.; Bishop, J.; Lowe, X. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 372, Issue 2 https://doi.org/10.1016/S0027-5107(96)00145-5	journal	December 1996
Semen quality and spermatozoal DNA integrity in survivors of childhood cancer: a case-control study Thomson, Angela B.; Campbell, Alastair J.; Irvine, D. Stewart The Lancet, Vol. 360, Issue 9330 https://doi.org/10.1016/S0140-6736(02)09606-X	journal	August 2002
Recovery of sperm production following radiation therapy for Hodgkin’s disease after induction chemotherapy with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) Dubey, Praveen; Wilson, Gene; Mathur, Kevin K. International Journal of Radiation OncologyBiologyPhysics, Vol. 46, Issue 3 https://doi.org/10.1016/S0360-3016(99)00338-7	journal	February 2000
Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age Sloter, Eddie D.; Marchetti, Francesco; Eskenazi, Brenda Fertility and Sterility, Vol. 87, Issue 5 https://doi.org/10.1016/j.fertnstert.2006.08.112	journal	May 2007
Effects of chemotherapy and radiotherapy on spermatogenesis in humans Meistrich, Marvin L. Fertility and Sterility, Vol. 100, Issue 5 https://doi.org/10.1016/j.fertnstert.2013.08.010	journal	November 2013
Impact of lymphoma treatments on spermatogenesis and sperm deoxyribonucleic acid: a multicenter prospective study from the CECOS network Bujan, Louis; Walschaerts, Marie; Brugnon, Florence Fertility and Sterility, Vol. 102, Issue 3 https://doi.org/10.1016/j.fertnstert.2014.06.008	journal	September 2014
Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network Martinez, Guillaume; Walschaerts, Marie; Le Mitouard, Marine Fertility and Sterility, Vol. 107, Issue 2 https://doi.org/10.1016/j.fertnstert.2016.10.001	journal	February 2017
Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d’Étude et de Conservation des Oeufs et du Sperme network Rives, Nathalie; Walschaerts, Marie; Setif, Véronique Fertility and Sterility, Vol. 107, Issue 3 https://doi.org/10.1016/j.fertnstert.2016.11.015	journal	March 2017
The overall rates of dominant and recessive lethal and visible mutation induced by spermatogonial X-irradiation of mice Lyon, Mary F.; Phillips, Rita J. S.; Searle, A. G. Genetical Research, Vol. 5, Issue 3 https://doi.org/10.1017/S0016672300034893	journal	November 1964
Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm Robbins, Wendie A.; Meistrich, Marvin L.; Moore, Dan Nature Genetics, Vol. 16, Issue 1 https://doi.org/10.1038/ng0597-74	journal	May 1997
Repair of radiation damage to DNA Willers, H.; Dahm-Daphi, J.; Powell, S. N. British Journal of Cancer, Vol. 90, Issue 7 https://doi.org/10.1038/sj.bjc.6601729	journal	March 2004
Three-probe fluorescence in situ hybridization to assess chromosome X, Y, and 8 aneuploidy in sperm of 14 men from two healthy groups: evidence for a paternal age effect on sperm aneuploidy Robbins, Wa; Baulch, Je; Moore, D. Reproduction, Fertility and Development, Vol. 7, Issue 4 https://doi.org/10.1071/RD9950799	journal	January 1995
Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse Marchetti, F.; Bishop, J. B.; Lowe, X. Proceedings of the National Academy of Sciences, Vol. 98, Issue 7 https://doi.org/10.1073/pnas.061404598	journal	March 2001
Multicolor FISH Analysis of Chromosomal Breaks, Duplications, Deletions, and Numerical Abnormalities in the Sperm of Healthy Men Sloter, Eddie D.; Lowe, Xiu; Moore, Dan H. The American Journal of Human Genetics, Vol. 67, Issue 4 https://doi.org/10.1086/303088	journal	October 2000
Meiotic Segregation, Recombination, and Gamete Aneuploidy Assessed in a t(1;10)(p22.1;q22.3) Reciprocal Translocation Carrier by Three- and Four-Probe Multicolor FISH in Sperm Hummelen, Paul Van; Manchester, David; Lowe, Xiu The American Journal of Human Genetics, Vol. 61, Issue 3 https://doi.org/10.1086/515516	journal	September 1997
Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients Schmid, T. E. Human Reproduction, Vol. 19, Issue 6 https://doi.org/10.1093/humrep/deh278	journal	April 2004
Etoposide induces chromosomal abnormalities in mouse spermatocytes and stem cell spermatogonia Marchetti, Francesco; Pearson, Francesca S.; Bishop, Jack B. Human Reproduction, Vol. 21, Issue 4 https://doi.org/10.1093/humrep/dei416	journal	November 2005
Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients Tempest, H. G.; Ko, E.; Chan, P. Human Reproduction, Vol. 23, Issue 2 https://doi.org/10.1093/humrep/dem389	journal	December 2007
New insights on the origin and relevance of aneuploidy in human spermatozoa Templado, C.; Uroz, L.; Estop, A. MHR: Basic science of reproductive medicine, Vol. 19, Issue 10 https://doi.org/10.1093/molehr/gat039	journal	May 2013
Paternally Transmitted Chromosomal Aberrations in Mouse Zygotes Determine Their Embryonic Fate1 Marchetti, Francesco; Bishop, Jack B.; Cosentino, Lidia Biology of Reproduction, Vol. 70, Issue 3 https://doi.org/10.1095/biolreprod.103.023044	journal	March 2004
Novel Stage Classification of Human Spermatogenesis Based on Acrosome Development1 Muciaccia, Barbara; Boitani, Carla; Berloco, B. Pasquale Biology of Reproduction, Vol. 89, Issue 3 https://doi.org/10.1095/biolreprod.113.111682	journal	September 2013
Spermatogenesis in Man: An Estimate of Its Duration Heller, C. G.; Clermont, Y. Science, Vol. 140, Issue 3563 https://doi.org/10.1126/science.140.3563.184	journal	April 1963
De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age Thomas, N. S.; Morris, J. K.; Baptista, J. Journal of Medical Genetics, Vol. 47, Issue 2 https://doi.org/10.1136/jmg.2009.069716	journal	July 2009
On the parental origin of de novo mutation in man. Chandley, A. C. Journal of Medical Genetics, Vol. 28, Issue 4 https://doi.org/10.1136/jmg.28.4.217	journal	April 1991
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions Liehr, Thomas; Schreyer, Isolde; Kuechler, Alma Molecular Cytogenetics, Vol. 11, Issue 1 https://doi.org/10.1186/s13039-018-0369-1	journal	March 2018
Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease. Meistrich, M. L.; Wilson, G.; Mathur, K. Journal of Clinical Oncology, Vol. 15, Issue 12 https://doi.org/10.1200/JCO.1997.15.12.3488	journal	December 1997
Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study Signorello, Lisa B.; Mulvihill, John J.; Green, Daniel M. Journal of Clinical Oncology, Vol. 30, Issue 3 https://doi.org/10.1200/JCO.2011.37.2938	journal	January 2012
Spermatogonial kinetics in humans Di Persio, Sara; Saracino, Rossana; Fera, Stefania Development, Vol. 144, Issue 19 https://doi.org/10.1242/dev.150284	journal	August 2017
Occupational Exposure to Benzene and Chromosomal Structural Aberrations in the Sperm of Chinese Men Marchetti, Francesco; Eskenazi, Brenda; Weldon, Rosana H. Environmental Health Perspectives, Vol. 120, Issue 2 https://doi.org/10.1289/ehp.1103921	journal	February 2012

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