A model for the function of sperm DNA degradation
Monika A. Ward A † and W. Steven Ward A B
+ Author Affiliations
- Author Affiliations
A 1960 East-West Road, Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA.
B To whom correspondence should be addressed. email: wward@hawaii.edu
Reproduction, Fertility and Development 16(5) 547-554 https://doi.org/10.1071/RD03072
Submitted: 7 October 2003 Accepted: 26 November 2003 Published: 22 July 2004
Abstract
In this review, we present our recent evidence suggesting, but not yet proving, that mammalian spermatozoa contain a mechanism by which they can digest their own DNA when exposed to a stressful environment. We discuss our recent data that demonstrate that when mammalian spermatozoa are treated in a variety of ways, the paternal chromosomes in the zygote, or the sperm DNA itself, are degraded into large, chromosome-sized fragments. These published data support the existence of nuclease activity in spermatozoa. We suggest that this nuclease activity is part of a mechanism the spermatozoon uses when it encounters a stressful environment to prevent fertilisation and to avoid the transmission of potentially damaged DNA to the embryo. We propose a model based on sperm chromatin structure by which this nuclease can digest the highly condensed sperm chromatin.
Acknowledgments
This work was supported by NIH Grant HD28501 to W. S. W. and the Harold K. Castle Foundation, the Hawaii State Biomedical Research Infrastructure Network (NIH P20 RR16467) and Victoria S. and Bradley L. Geist Foundation (20031970) grants to M.A.W.
References
Asada, M. , Wei, H. , Nagayama, R. , Tetsuka, M. , Ishikawa, H. , Ohsumi, S. , and Fukui, Y. (2001). An attempt at intracytoplasmic sperm injection of frozen–thawed minke whale (Balaenoptera bonaerensis) oocytes. Zygote 9, 299–307.
| PubMed |
Barone, J. G. , De Lara, J. , Cummings, K. B. , and Ward, W. S. (1994). DNA organization in human spermatozoa. J. Androl. 15, 139–144.
| PubMed |
Bhowmick, S. , Zhu, L. , McGinnis, L. , Lawitts, J. , Nath, B. D. , Toner, M. , and Biggers, J. (2003). Desiccation tolerance of spermatozoa dried at ambient temperature: production of fetal mice. Biol. Reprod. 68, 1779–1786.
| PubMed |
Brewer, L. R. , Corzett, M. , and Balhorn, R. (1999). Protamine-induced condensation and decondensation of the same DNA molecule. Science 286, 120–123.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Brewer, L. , Corzett, M. , and Balhorn, R. (2002). Condensation of DNA by spermatid basic nuclear proteins. J. Biol. Chem. 277, 38895–38900.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Choudhary, S. K. , Wykes, S. M. , Kramer, J. A. , Mohamed, A. N. , Koppitch, F. , Nelson, J. E. , and Krawetz, S. A. (1995). A haploid expressed gene cluster exists as a single chromatin domain in human sperm. J. Biol. Chem. 270, 8755–8762.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cox, L. J. , Larman, M. G. , Saunders, C. M. , Hashimoto, K. , Swann, K. , and Lai, F. A. (2002). Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes. Reproduction 124, 611–623.
| PubMed |
Fawcett, D. W. (1970). A comparative view of sperm ultrastructure. Biol. Reprod. 2, 90–127.
| PubMed |
Gineitis, A. A. , Zalenskaya, I. A. , Yau, P. M. , Bradbury, E. M. , and Zalensky, A. O. (2000). Human sperm telomere-binding complex involves histone H2B and secures telomere membrane attachment. J. Cell Biol. 151, 1591–1598.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gonzalez-Estrella, J. A. , Coney, P. , Ostash, K. , and Karabinus, D. (1994). Dithiothreitol effects on the viscosity and quality of human semen. Fertil. Steril. 62, 1238–1243.
| PubMed |
Haaf, T. , and Ward, D. C. (1995). Higher order nuclear structure in mammalian sperm revealed by in situ hybridization and extended chromatin fibers. Exp. Cell Res. 219, 604–611.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hud, N. V. , Allen, M. J. , Downing, K. H. , Lee, J. , and Balhorn, R. (1993). Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy. Biochem. Biophys. Res. Commun. 193, 1347–1354.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Hud, N. V. , Downing, K. H. , and Balhorn, R. (1995). A constant radius of curvature model for the organization of DNA in toroidal condensates. Proc. Natl Acad. Sci. USA 92, 3581–3585.
| PubMed |
Kalandadze, A. G. , Bushara, S. A. , Vasetskii, E. S. , and Razin, S. V. (1989). Characteristics of DNA sequences in the sites of permanent attachment to the nuclear matrix located in the vicinity of replication initiation site. Mol. Biol. (Mosk.) 23, 1309–1320.
| PubMed |
Kalandadze, A. G. , Bushara, S. A. , Vassetzky, Y. S. , and Razin, S. V. (1990). Characterization of DNA pattern in the site of permanent attachment to the nuclear matrix located in the vicinity of replication origin. Biochem. Biophys. Res. Commun. 168, 9–15.
| PubMed |
Kasai, T. , Hoshi, K. , and Yanagimachi, R. (1999). Effect of sperm immobilisation and demembranation on the oocyte activation rate in the mouse. Zygote 7, 187–193.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Keskintepe, L. , Pacholczyk, G. , Machnicka, A. , Norris, K. , Curuk, M. A. , Khan, I. , and Brackett, B. G. (2002). Bovine blastocyst development from oocytes injected with freeze-dried spermatozoa. Biol. Reprod. 67, 409–415.
| PubMed |
Kimura, Y. , Yanagimachi, R. , Kuretake, S. , Bortkiewicz, H. , Perry, A. C. , and Yanagimachi, H. (1998). Analysis of mouse oocyte activation suggests the involvement of sperm perinuclear material. Biol. Reprod. 58, 1407–1415.
| PubMed |
Klaus, A. V. , McCarrey, J. R. , Farkas, A. , and Ward, W. S. (2001). Changes in DNA loop domain structure during spermatogenesis and embryogenesis in the Syrian golden hamster. Biol. Reprod. 64, 1297–1306.
| PubMed |
Kuretake, S. , Kimura, Y. , Hoshi, K. , and Yanagimachi, R. (1996). Fertilization and development of mouse oocytes injected with isolated sperm heads. Biol. Reprod. 55, 789–795.
| PubMed |
Kusakabe, H. , Szczygiel, M. A. , Whittingham, D. G. , and Yanagimachi, R. (2001). Maintenance of genetic integrity in frozen and freeze-dried mouse spermatozoa. Proc. Natl Acad. Sci. USA 98, 13501–13506.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lawen, A. (2003). Apoptosis – an introduction. Bioessays 25, 888–896.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Li, T. K. , Chen, A. Y. , Yu, C. , Mao, Y. , Wang, H. , and Liu, L. F. (1999). Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress. Genes Dev. 13, 1553–1560.
| PubMed |
Maione, B. , Pittoggi, C. , Achene, L. , Lorenzini, R. , and Spadafora, C. (1997). Activation of endogenous nucleases in mature sperm cells upon interaction with exogenous DNA. DNA Cell Biol. 16, 1087–1097.
| PubMed |
Mohar, I. , Szczygiel, M. A. , Yanagimachi, R. , and Ward, W. S. (2002). Sperm nuclear halos can transform into normal chromosomes after injection into oocytes. Mol. Reprod. Dev. 62, 416–420.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Nadel, B. , de Lara, J. , Finkernagel, S. W. , and Ward, W. S. (1995). Cell-specific organization of the 5S ribosomal RNA gene cluster DNA loop domains in spermatozoa and somatic cells. Biol. Reprod. 53, 1222–1228.
| PubMed |
Perry, A. C. , Wakayama, T. , Kishikawa, H. , Kasai, T. , Okabe, M. , Toyoda, Y. , and Yanagimachi, R. (1999). Mammalian transgenesis by intracytoplasmic sperm injection. Science 284, 1180–1183.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Pienta, K. J. , Getzenberg, R. H. , and Coffey, D. S. (1991). Cell structure and DNA organization. Crit. Rev. Eukaryot. Gene Expr. 1, 355–385.
| PubMed |
Pittoggi, C. , Zaccagnini, G. , Giordano, R. , Magnano, A. R. , Baccetti, B. , Lorenzini, R. , and Spadafora, C. (2000). Nucleosomal domains of mouse spermatozoa chromatin as potential sites for retroposition and foreign DNA integration. Mol. Reprod. Dev. 56, 248–251.
| Crossref | GoogleScholarGoogle Scholar |
Puwaravutipanich, T. , and Panyim, S. (1975). The nuclear basic proteins of human testes and ejaculated spermatozoa. Exp. Cell Res. 90, 153–158.
| PubMed |
Rao, B. , and David, G. (1984). Improved recovery of post-thaw motility and vitality of human spermatozoa cryopreserved in the presence of dithiothreitol. Cryobiology 21, 536–541.
| PubMed |
Rho, G. J. , Kawarsky, S. , Johnson, W. H. , Kochhar, K. , and Betteridge, K. J. (1998). Sperm and oocyte treatments to improve the formation of male and female pronuclei and subsequent development following intracytoplasmic sperm injection into bovine oocytes. Biol. Reprod. 59, 918–924.
| PubMed |
Saunders, C. M. , Larman, M. G. , Parrington, J. , Cox, L. J. , Royse, J. , Blayney, L. M. , Swann, K. , and Lai, F. A. (2002). PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development 129, 3533–3544.
| PubMed |
Sawetawan, C. , Bruns, E. S. , and Prins, G. S. (1993). Improvement of post-thaw sperm motility in poor quality human semen. Fertil. Steril. 60, 706–710.
| PubMed |
Solovyan, V. T. , Bezvenyuk, Z. A. , Salminen, A. , Austin, C. A. , and Courtney, M. J. (2002). The role of topoisomerase II in the excision of DNA loop domains during apoptosis. J. Biol. Chem. 277, 21458–21467.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Sotolongo, B. , and Ward, W. S. (2001). DNA loop domain organization: the three dimensional genomic code. J. Cell. Biochem Suppl 35, 23–26.
Sotolongo, B. , Lino, E. , and Ward, W. S. (2003). Ability of hamster spermatozoa to digest their own DNA. Biol. Reprod. 69, 2029–2035.
| PubMed |
Suttner, R. , Zakhartchenko, V. , Stojkovic, P. , Muller, S. , Alberio, R. , Medjugorac, I. , Brem, G. , Wolf, E. , and Stojkovic, M. (2000). Intracytoplasmic sperm injection in bovine: effects of oocyte activation, sperm pretreatment and injection technique. Theriogenology 54, 935–948.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Szczygiel, M. A. , and Ward, W. S. (2002). Combination of dithiothreitol and detergent treatment of spermatozoa causes paternal chromosomal damage. Biol. Reprod. 67, 1532–1537.
| PubMed |
Szczygiel, M. A. , Kusakabe, H. , Yanagimachi, R. , and Whittingham, D. G. (2002). Intracytoplasmic sperm injection is more efficient than in vitro fertilization for generating mouse embryos from cryopreserved spermatozoa. Biol. Reprod. 67, 1278–1284.
| PubMed |
Szczygiel, M. A. , Moisyadi, S. , and Ward, W. S. (2003). Expression of foreign DNA is associated with paternal chromosome degradation in ICSI-mediated transgenesis in the mouse. Biol. Reprod. 68, 1903–1910.
| PubMed |
Tateno, H. , and Kamiguchi, Y. (1999). Dithiothreitol induces sperm nuclear decondensation and protects against chromosome damage during male pronuclear formation in hybrid zygotes between Chinese hamster spermatozoa and Syrian hamster oocytes. Zygote 7, 321–327.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Tateno, H. , Kimura, Y. , and Yanagimachi, R. (2000). Sonication per se is not as deleterious to sperm chromosomes as previously inferred. Biol. Reprod. 63, 341–346.
| PubMed |
Twigg, J. , Irvine, D. S. , Houston, P. , Fulton, N. , Michael, L. , and Aitken, R. J. (1998a). Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol. Hum. Reprod. 4, 439–445.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Twigg, J. P. , Irvine, D. S. , and Aitken, R. J. (1998b). Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Hum. Reprod. 13, 1864–1871.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wakayama, T. , and Yanagimachi, R. (1998). Development of normal mice from oocytes injected with freeze-dried spermatozoa. Nat. Biotechnol. 16, 639–641.
| PubMed |
Wakayama, T. , Whittingham, D. G. , and Yanagimachi, R. (1998). Production of normal offspring from mouse oocytes injected with spermatozoa cryopreserved with or without cryoprotection. J. Reprod. Fertil. 112, 11–17.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ward, M. A. , Kaneko, T. , Kusakabe, H. , Biggers, J. D. , Whittingham, D. G. , and Yanagimachi, R. (2003). Long-term preservation of mouse spermatozoa after freeze-drying and freezing without cryoprotection. Biol. Reprod. 69, 2100–2108.
| PubMed |
Ward, W. S. (1993). Deoxyribonucleic acid loop domain tertiary structure in mammalian spermatozoa. Biol. Reprod. 48, 1193–1201.
| PubMed |
Ward, W. S. , and Coffey, D. S. (1990). Specific organization of genes in relation to the sperm nuclear matrix. Biochem. Biophys. Res. Commun. 173, 20–25.
| PubMed |
Ward, W. S. , Partin, A. W. , and Coffey, D. S. (1989). DNA loop domains in mammalian spermatozoa. Chromosoma 98, 153–159.
| PubMed |
Ward, W. S. , Kimura, Y. , and Yanagimachi, R. (1999). An intact sperm nuclear matrix may be necessary for the mouse paternal genome to participate in embryonic development. Biol. Reprod. 60, 702–706.
| PubMed |
Wykes, S. M. , and Krawetz, S. A. (2003). The structural organization of sperm chromatin. J. Biol. Chem. 278, 29471–29477.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zalensky, A. O. , Allen, M. J. , Kobayashi, A. , Zalenskaya, I. A. , Balhorn, R. , and Bradbury, E. M. (1995). Well-defined genome architecture in the human sperm nucleus. Chromosoma 103, 577–590.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zalensky, A. O. , Tomilin, N. V. , Zalenskaya, I. A. , Teplitz, R. L. , and Bradbury, E. M. (1997). Telomere–telomere interactions and candidate telomere binding protein(s) in mammalian sperm cells. Exp. Cell Res. 232, 29–41.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Zalensky, A. O. , Siino, J. S. , Gineitis, A. A. , Zalenskaya, I. A. , Tomilin, N. V. , Yau, P. , and Bradbury, E. M. (2002). Human testis/sperm-specific histone H2B (hTSH2B). Molecular cloning and characterization. J. Biol. Chem. 277, 43474–43480.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
† Monika A. Ward previously published under the name of Monika A. Szczygiel.
