Sperm epigenetic profile and risk of cancer
More details
Hide details
Diagnostic Techniques Unit, Faculty of Nursing and Health Sciences, Medical University, Lublin, Poland
Artur Wdowiak   

Diagnostic Techniques Unit, Faculty of Nursing and Health Sciences, Medical University, Lublin, Poland
J Pre Clin Clin Res. 2014;8(2):67–70
Introduction and objective:
The integrity, stability and composition of sperm chromatin are of great importance in the fertilizing potential of male gametes and their capacity to support normal embryonic development. In this study, the author presents the current state of knowledge about the sperm epigenetic profile and risk of cancer.

Abbreviated description of the state of knowledge:
The obtaining of pregnancy and the state of health of the baby depends on the quality of the genetic material of both the female and the male. Health behaviours and environmental factors directly affect the quality of sperm, as well as the human egg cell and, consequently, on the reproductive capabilities, the course of pregnancy and the state of the newborn. There exist two thoroughly investigated epigenetic modifications: DNA methylation and histone modifications. The process of DNA methylation can be also a fundamental factor contributing to the development of cancer, where epigenotype undergoes significant modifications. When considering numerous DNA aberrations in the male gamete, the most commonly encountered is DNA fragmentation, particularly in infertile subjects. Surprisingly, an intracytoplasmatic sperm injection study of mice oocytes, using spermatozoa with a high DNA Fragmentation Index (DFI), revealed that a considerable percentage of adults born as a result of this method, showed a significant increase in the incidence of abnormal behavioural tests, malformations, cancer and signs of premature aging.

The issue of assisted procreation raises the need to look for an appropriate treatment for males with sperm chromatin abnormalities. As a result, the fight against smoking addiction becomes the obvious necessity. Moreover, the reasonable solution nowadays seems to be supplementation with micronutrients and folic acid. It has been proved that the process of DNA fragmentation is a phenomenon that intensifies over time. Therefore, there should be a pursuance for, as close as possible, to the moment of ejaculation, application of semen to reproductive techniques. Finally, epigenetic changes are suspected of being one of the factors responsible for the deterioration of male sperm parameters observed in recent decades.

Albertini DF. Confronting the fissions and fusions of human fertilization. J Assist Reprod Genet. 2014; 31(5): 507–508.
Nel-Themaat L, Nagy ZP. A review of the promises and pitfalls of oocyte and embryo metabolomics. Placenta. 2011; 32: 257–263.
Whitelaw N, Bhattacharya S, Hoad G, Horgan GW, Hamilton M, Haggarty P. Epigenetic status in the offspring of spontaneous and assisted conception. Hum Reprod. 2014; 5(8).
Erenpreiss J, Spano M, Erenpreisa J, et al. Sperm chromatin structure and male fertility: biological and clinical aspects. Asian J Androl 2006; 8: 11–29.
Hofmann N, Hilscher B.Use of aniline blue to assess chromatin condensation in morphologically normal spermatozoa in normal and infertile men. Hum Reprod. 1991; 6(7): 979–982.
Tamburrino L, Marchiani S, Montoya M, Elia Marino F, Natali I, et al. Mechanisms and clinical correlates of sperm DNA damage. Asian J Androl. 2012; 14(1): 24–31.
Perdrix A, Rives N. Motile sperm organelle morphology examination (MSOME) and sperm head vacuoles: state of the art in 2013. Hum Reprod Update. 2013; 19(5): 527–541.
Tremellen K. Oxidative stress and male infertility – a clinical perspective. Human Reproduction Update 2008; 14: 243–258.
Kurus M, Karakaya C, Karalok MH, To G, Johnson J. The control of oocyte survival by intrinsic and extrinsic factors. Adv Exp Med Biol. 2013; 761: 7–18.
Bird A. The essentials of DNA methylation. Cell. 1992; 70: 5–8.
Mukhopadhyay P, Rezzoug F, Kaikus J, Greene RM, Pisano MM. Alcohol modulates expression of DNA methyltranferases and methyl CpG-/CpG domain- binding proteins in murine embryonic fibroblasts. Reproduct Toxicol. 2013; 1: 1–19.
Jenuwein T, Allis CD. Translating the histone code. Science. 2001; 293: 1074–1080.
Jabłońska J, Jesionek-Kupnicka D. Zmiany epigentyczne w nowotworach. Onkologia Polska 2004; 7(4): 181–185 (in Polish).
Salozhin SV, Prokhorchuk EB, Georgiev GP. Methylation of DNA-One of the major epigenetic markers. Biochemistry (Moscow) 2005; 70(5): 525–532.
Sulewska A, Niklinska W, Kozlowski M, Minarowski L, Naumnik W, Niklinski J, Dabrowska K, Chyczewski. Detection of DNA methylation in eucaryotic cells. L Folia Histochem Cytobiol. 2007; 45(4): 315–324.
Tunc O, Tremellen K. Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet. 2009; 26(9– 10): 537–544.
Percipalle P. New insights into co-transcriptional sorting of mRNA for cytoplasmic transport during development. Semin Cell Dev Biol. 2014; 32: 55–62.
Paradowska-Dogan A, Fernandez A, Bergmann M, Kretzer K, Mallidis C, Vieweg M, Waliszewski P, Zitzmann M, Weidner W, Steger K, Kliesch S. Protamine mRNA ratio in stallion spermatozoa correlates with mare fecundity. Andrology 2014; 2(4): 521–530.
Fritz-Niggli H, Schaeppi-Buechi C.Adaptive response to dominant lethality of mature (class A) and immature (class B) oocytes of D. melanogaster to low doses of ionizing radiation: effects in repair-proficient (yw) and repair-deficient strains (mei 41D5 and mus 302D1). Int J Radiat Biol. 1991; 59(1): 175–184.
Ashwood-Smith MJ, Edwards RG, DNA repair by oocytes. Mol Hum Reprod. 1996; 2(1): 46–51.
Barber RC, Hickenbotham P, Hatch T, Kelly D, Topchiy N, et al. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene 2006; 25(56): 7336–7342.
Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005; 308(5727): 1466–1469.
Bufton L, Bruns GA, Magenis RE, Tomar D, Shaw D, Brook D, Litt M. Four restriction fragment length polymorphisms revealed by probes from a single cosmid map to chromosome 19. Am J Hum Genet. 1986; 38(4): 447–460.
Fernández-González R, Moreira PN, Pérez-Crespo M, Sánchez-Martín M, Ramirez MA, et al. Long-term effects of mouse intracytoplasmic sperm injection with DNA-fragmented sperm on health and behavior of adult offspring. Biol Reprod. 2008; 78: 761–772.
Manicardi GC, Bianchi PG, Pantano S, Azzoni P, Bizzaro D, Bianchi U, Sakkas D.Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility.Biol Reprod. 1995; 52(4): 864–867.
Ji BT, Shu XO, Linet MS, Zheng W, Wacholder S, Gao YT, Ying DM, Jin F. Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers. J Natl Cancer Inst. 1997; 89(3): 238–244.
Sorahan T, Lancashire RJ, Hultén MA, Peck I, Stewart AM. Childhood cancer and parental use of tobacco: deaths from 1953 to 1955. Br J Cancer. 1997; 75(1): 134–138.
Wdowiak A, LewickaM, Plewka K, Bakalczuk G. Nicotinism and quality of embryos obtained in in-vitro fertilization programmes. Ann Agric Environ Med. 2013; 20(1): 82–85.
Dubrova YE. Radiation-induced transgenerational instability. Oncogene 2003; 22(45): 7087–7093.
Mohr U, Dasenbrock C, Tillmann T, Kohler M, Kamino K, Hagemann G, Morawietz G, Campo E, Cazorla M, Fernandez P, Hernandez L, Cardesa A, Tomatis L. Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice. Carcinogenesis 1999; 20(2): 325–332.
Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013; 288(1): 191–199.
Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH.A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007; 16(7): 1325–1329.
Alvarez Sedó C, Barros MA. Uriondo Boudri H. Rougier N, Papier S, Nodar F. Changes in DNA fragmentation during sperm preparation for ICSI over time 109. IBRA Assist Reprod. 2013; 17: 109–114.