İNFERTİL ÇİFTLERDE SPERM GENOMİK STABİLİTESİNİN BELİRLENMESİNDE DNA FRAGMANTASYONU ANALİZ YÖNTEMLERİ

Çevresel stres, gen mutasyonları ve kromozomal anormalliklerin tamamı, spermatogenez sırasındaki tüm aşamaları etkileyebilir, bu da sonuçta, infertiliteye sebep olan anormal kromatin yapısına yol açabilir. DNA hasarlı sperm taşıyan kişilerde tüp bebek başarısızlığı da tekrarlayan gebelik kaybı da sık görülmektedir. Ayrıca, DNA fragmantasyon bozukluğu olan spermle döllenmiş olan yumurtalardan oluşan embriyolar gebelik dönemini sorunsuz atlatmış olsa bile, teorik olarak konjenital malformasyonlar ve çocukluk çağı kanserleri gelişimi açısından risk altındadır. Bu nedenle yardımcı üreme teknikleri uygulanırken tedavi öncesi sperm DNA fragmantasyon testi uygulanması ve en iyi hücrelerin seçilmesi hayati önem taşımaktadır. Günümüzde kullanılan çok farklı sperm DNA hasarı belirleme yöntemleri mevcuttur. Bu derlemenin amacı sperm DNA’sında oluşan hasar ve fragmantasyonları test etmek için geliştirilen yöntemlerin klinik kullanımdaki yerleri ile birlikte değerlendirmektir. 

Sperm DNA Fragmantation Analysis Methods in Infertile Couples for Assessing Genomic Instability

Environmental stress, gene mutations, and chromosomal abnormalities can all affect the steps of spermatogenesis, which in turn may lead to abnormal chromatin structure causing infertility. In couples with DNA-damaged sperm, in vitro fertilization failure may also frequently be seen as recurrent pregnancy loss. In addition, embryos which are fertilized with sperm which have DNA fragmentation disorder are under the risk of developing congenital malformations or childhood cancers, even if the embryos have survived the pregnancy period without any problems. Therefore, sperm DNA fragmentation test before the and selection of the best cells is vital when assisted reproductive techniques are applied. There are many different methods of detecting sperm DNA damage used today. The aim of this review is to evaluate the methods developed to test the damage and fragmentation of sperm DNA in clinical practice.
Keywords:

Infertility, Sperm,

___

  • Agarwal, A., Virk, G., Ong, C., Plessis, S. (2014). Effect of Oxidative Stress on Male Reproduction. World J Mens Health, 32: 1–17.
  • Alvarez, J.G. (2003). DNA fragmentation in humanspermatozoa: significance in the diagnosis and treatment of infertility. Minerva Ginecol, 55:233-9.
  • Arnon, J., Meirow, D., Lewis-Roness, H., Ornoy, A. (2001). Genetic and teratogenic effects of cancer treatments on gametes and embryos.Hum Reprod Update. 7:394-403
  • Belva, F., Bonduelle, M., Roelants, M., Michielsen, D., et al. (2016). Semen quality of young adult ICSI offspring: the first results. Hum Reprod, 31, 2811-20.
  • Bradley, C.K., McArthur, S.J., Gee, A. et al. (2016). Intervention improve sassisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm dna fragmentation: a retrospectiveanalysis. Andrology, 4:903-10.
  • Carrell, D.T., Liu, L. (2001). Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl, 22:604-10.
  • Cissen, M., Wely, M.V., Scholten, I., Mansell, S.,et al. (2016). Measuring sperm dna fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS One, 11(11), e0165125.
  • Donald, P., Everson, D.P. (2006). Clinical aspects of sperm DNA fragmentation detection and male infertility, Theriogenology, 65(5); 979-991.
  • Erenpreiss, J., Hlevicka, S., Zalkalns, J., Erenpreisa, J. (2002). Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples.J Androl. 23 :717-23.
  • Erenpreiss, J., Jepson, K., Giwercman, A., Tsarev, I., et al. (2004). Toluidine blue cytometry test for sperm DNA conformation: comparison with the fowcytometric sperm chromatin structure and TUNEL assays. Hum Reprod,19, 2277-82.
  • Evenson D.P., Wixon, R. (2006). Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology, 65(5), 979-91.
  • Gatewood, J.M., Cook, G.R., Balhorn, R., Bradbury, E.M., Schmid, C.W. (1987). Sequence-specific packaging of dna in human sperm chromatin.Science, 236:962-4.
  • Gelbaya, T.A., Potdar, N., Jeve, Y.B., Nardo, L.G. (2014). Definition and epidemiology of unexplained infertility. ObstetGynecolSurv, 69:109-15.
  • Gosalvez, J., Gonzalez-Martinez, M., Lopez-Fernandez, C., et al. (2011). Shorter abstinence decreases sperm deoxyribonucleic acid fragmentation in ejaculate. Fertil Steril, 96:1083-6.
  • Güneş, S., Sevgili, E., Aşçı, R. (2013). Sperm DNA Hasarı Mekanizmaları ve Değerlendirme Yöntemleri. Turkiye Klinikleri J Urology 4(3):107-14
  • Haines, G., Marples, B., Daniel, P., Morris, I. (1998). DNA damage in human and mouse spermatozoa after in vitro-irradiation assessed by the komet assay.Adv Exp Med Biol, 444:79-91.
  • Inhorn, M.C. & Patrizio, P. (2015). Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update, 21(4), 411-26.
  • Irvine, D.S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13: 33-44.
  • Kierszenbaum, A.L. (2001). Transition nuclear proteins during spermiogenesis: unrepaired DNA breaks not allowed. Mol Reprod Dev. 58:357-8.
  • Kobayashi, H., Larson, K., Sharma, R.K., Nelson, D.R., et al (2001). Evenson DP, Toma H, Thomas AJ, Agarwal A. DNA damage in patients with untreated cancer as measured by the sperm chromatin structure assay.Fertil Steril, 75:469-75.
  • Kosower, N.S., Katayose, H., Yanagimachi, R. (1992). Thiol-disulfide status and acridine orange fluorescence of mammalian sperm nuclei. J Androl, 13:342-8.
  • Koyuncu, H. (2011). Sperm DNA Hasarı Tespit Yöntemleri, Turk Urol Sem 2: 18-23
  • Kucuk, N. (2018). Sperm DNA and detection of DNA fragmentations in sperm, Turk J Urol, 44: 1-5
  • Kupker, W., Schwinger, E., Hiort, 0 ., Ludwing, M., et al. (1999). Genetics of male subfertility: consequences for the clinical work-up. Hum Reprod. 14:1, 24-37.
  • Labbe, C., Martoriati, A., Devaux, A., Maisse, G. (2001). Effect of sperm cryopreservation on sperm DNA stability and progeny development in rainbow trout.Mol Reprod Dev. 60:397-404.
  • Majzoub, A., Agarwal, A., Cho, C.L., Esteves, S. (2017). Sperm dna fragmentation testing: a crosssectional survey on current practices of fertility specialists. Trans Androl Urol, 6:710–9.
  • Manicardi, G.C., Bianchi, P.G., Pantano, S. et al. (1995). Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship of chromomycine A3 acessibility. Biol Reprod, 52:864-7.
  • Morris, I.D. (2002). Sperm DNA damage and cancer treatment.Int J Androl. 25: 255-61.
  • Muratori, M., Marchiani, S., Maggi, M., Forti, G., et al. (2006). Origin and biological significance of DNA fragmentation in human spermatozoa. Front Biosci. 11:1491-9.
  • Muriel, L., Garrido, N., Fernandez, J.L., Remohi, J., et al. (2006). Value of the sperm deoxyribonucleic acid fragmentation level, as measured by the sperm chromatin dispersion test, in the outcome of in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril, 85:371–83
  • Ordueri, E., Özenci, Ç.Ç. (2013). Sperm nukleusu ve nüklear matriks: Parental genomu taşıyan kargodan fazlası, Androloji Bülteni, 129-132.
  • Paul, C., Povey, J.E., Lawrence, N.J., Selfridge, J., et al. (2007). Deletion of genes implicated in protecting the integrity of male germ cells has differential effects on the incidence of DNA breaks and germ cell loss.PLoS One. 2:1371-10
  • Potts, R.J., Newbury, C.J., Smith, G., Notarianni, L.J., et al.(1999). Sperm chromatin damage associated with male smoking.Mutat Res. 423:103-11.
  • Rahiminia, T., Hosseini, A., Anvari, M., Ghasemi-Esmailabad, S., et al. (2017). Modern human sperm freezing: Effect on DNA, chromatin and acrosome integrity. Taiwan J Obstet Gynecol. 56:472-76.
  • Robbins., D.J., Coleman, M.S. (1988). Initiatorrole of double stranded DNA in terminal transferase catalyzed polymerization reactions.Nucleic Acids Res 16:2943–57
  • Rui, B.R., Angrimani, D., Bicudo, L.C., Losano, J., et al. (2018). A fast, low-cost and efficient method for the diagnosis of sperm DNA fragmentation in several species. Reprod Domest Anim, 53, 171-175.
  • Sakkas, D., Seli, E., Bizzaro, D., Tarozzi, N., et al. (2003). Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis. Reprod Biomed Online. 7:428-32.
  • Saleh, R.A., Agarwal, A., Nada, E.A., El-Tonsy, et al. (2003). Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility.Fertil Steril. 79 :1597-605.
  • Shen, H.M., Ong, C.N. (2000). Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Rad Biol Med 28: 529-536.
  • Singh NP, Muller CH, Berger RE. (2003). Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril 80: 1420-1430.
  • Sinha, Hikim, A.P., Swerdloff, R.S. (1999). Hormonal and genetic control of germ cell apoptosis in the testis.Rev Reprod. 4:38-47.
  • Turk, G., Aksu, E.H., Bozkurt, T. (2006). Spermatozooon DNA’sı hasarı, FÜ Sağlık Bil. Dergisi, 20(1): 85-95.
  • Twigg, J., Irvine, D.S., Houston, P., Fulton, N., et al. (1998). Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol Hum Reprod 4:439-45
  • Ward, W.S., Coffey, D.S. (1991). DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells.Biol Reprod. 44:569-74.
  • Yiğit, A. (2015). IUI olgularında sperm fonksiyon testlerinin gebeliği öngörmedeki değeri. Yüksek Lisans Tezi, Yeni Yüzyıl Üniversitesi Sağlık Bilimleri Enstitüsü.
  • Zini, A., de Lamirande, E., Gagnon, C. (1993). Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa.Int J Androl. 16:183-8.
  • Zini, A., Jamal, W., Cowan, L. & Al-Hathal, N. (2011). Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet, 28(5), 391-7.