Main Article Content
Male infertility; Marker chromosome; Azoopermia
Background and objective
A small supernumerary marker chromosome (sSMC) is a rare structurally abnormal chromosome in which no part can be identified by conventional cytogenetic banding technique. There is little known about the association of marker chromosomes with male infertility. We performed a molecular cyto-genetic characterization sSMCs and investigated their association with male infertility.
Among 4230 infertile male patients who underwent cytogenetic analyses from January 2008 to December 2018, the records of 15 patients who were diagnosed with sSMCs were reviewed. After ini-tial infertility evaluation, the patients received additional genetic tests including G-bands by trypsin using Giemsa (GTG-banding), Nucleolar organizer region (NOR) banding, Fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) analyses to further char-acterize and identify the origin of their marker chromosome. Testis biopsy was performed for the azoospermic patients to evaluate spermatogenic status.
Among 15 infertile males with sSMCs, eight had nonobstructive azoospermia, five had severe oligozo-ospermia, and two had sperm concentrations above the lower normal limit. The marker chromosomes were identified as Y ring chromosomes (n = 8), an isodicentric Y chromosome (n = 1), a neocen-tromere Y chromosome (n = 1), a derivative chromosome 1 (n = 1), and an acrocentric short arms (n = 4).
Marker chromosomes appear to be a rare genetic cause of male infertility. Additional cytogenetic tests, including NOR banding, FISH, and aCGH, could help to characterize the origin of the marker chromosome. Appropriate genetic counseling for couples with infertility caused by a marker chromo-some should be recommended.
2. Ferlin A, Raicu F, Gatta V, et al. Male infertility: Role of genetic background. Reprod Biomed Online 2007;14:734–45. https://doi.org/10.1016/ S1472-6483(10)60677-3
3. Carrell DT, De Jonge C, Lamb DJ. The genetics of male infertility: A field of study whose time is now. Arch Androl 2006;52:269–74. https://doi. org/10.1080/01485010500503603
4. O'Flynn O'Brien KL, Varghese AC, Agarwal A. The genetic causes of male factor infertility: A review. Fertil Steril 2010;93:1–12. https://doi. org/10.1016/j.fertnstert.2009.10.045
5. Silber SJ, Repping S. Transmission of male infertility to future generations: Lessons from the Y chromosome. Hum Reprod Update 2002;8:217– 29. https://doi.org/10.1093/humupd/8.3.217
6. Liehr T, Weise A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 2007;19(5): 719–31.
7. Jiang Y, Yue F, Wang R, et al. Molecular cyto-genic characterization of an isodicentric Yq and a neocentric isochromosome Yp in an azoospermic male. Mol Med Rep 2020;21:918–92. https://doi. org/10.3892/mmr.2019.10883
8. Brugh VM 3rd, Maduro MR, Lamb DJ. Genetic disorders and infertility. Urol Clin North Am 2003;30:143–52. https://doi.org/10.1016/S0094-0143(02)00112-X
9. Liehr T, Claussen U, Starke H. Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 2004;107:55–67. https:// doi.org/10.1159/000079572
10. Song SH, Park SH, Shin E, et al. Male infertility associated with a supernumerary marker chromosome. World J Mens Health 2017;35:205–8. http:// dx.doi.org/10.5534/wjmh.17015
11. Koç A, Onur SO, Ergün MA, et al. Supernumerary marker chromosome 15 in a male with azoospermia and open bite deformity. Asian J Androl 2009;11:617–22. http://doi.org/10.1038/aja.2009.37
12. Manvelyan M, Riegel M, Santos M, et al. Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: Detailed molecular cytogenetic charac-terization and review of the literature. Int J Mol Med 2008;21:705–14.
13. Yu X-W, Wei Z-T, Jiang Y-T, et al. Y chromosome azoospermia factor region microdeletions and transmission characteristics in azoospermic and severe oligozoospermic patients. Int J Clin Exp Med 2015;8:14634–46.
14. Giacone F, Cannarella R, Mongioì LM, et al. Epigenetics of male fertility: Effects on assisted reproductive techniques. World J Mens Health 2019;37:148–56. http://dx.doi.org/10.5534/ wjmh.180071
15. Carrell DT. Contributions of spermatozoa to embryogenesis: Assays to evaluate their genetic and epigenetic fitness. Reprod Biomed Online 2008;16:474–84. https://doi.org/10.1016/S1472-6483(10)60454-3
16. Aston KI, Carrell DT. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl 2009;30:711–25. https://doi.org/10.2164/ jandrol.109.007971