Journal of Kerman University of Medical Sciences

Current Issue

By Issue

By Author

Author Index

Keyword Index

About Journal

Aims and Scope

JKMU Ethical Policies

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Metric

Editorial Policies

Data Sharing Policy

Investigation of Cytogenetic Abnormalities in Infertile Men with Idiopathic Spermatogenesis Disorder

Document Type : Original Article

Authors

1 Department of Urology, Kerman University of Medical Sciences, Kerman, Iran

2 Department of Urology, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Dermatology, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background: Infertility is one of the most common sexual health problems in the world affecting around 15% of couples. Males are responsible for the main cause of infertility in 50% of infertile couples, and the results of sperm analysis are abnormal in 25% of infertile men without any known etiology (i.e., idiopathic male infertility), where clinical history, physical examination, and hormonal analyses usually render normal results. Advances in various biomedical fields have allowed researchers to determine the role of interactions between genetic and environmental factors in the pathogenesis of infertility. Therefore, this study aimed to investigate cytogenetic abnormalities in men with idiopathic infertility.
Methods: This cross-sectional descriptive-analytical study was conducted on 135 infertile men (aged between 18 and 45 years) whose spouses seemed healthy in terms of fertility and were aged<35 years old. The patients initially underwent clinical examinations and paraclinical tests (hormonal tests, including FSH, LH, and testosterone). Spermogram was performed twice with an interval of 2 weeks following the standard criteria published by the World Health Organization (WHO), according to which men with known causes of infertility and obstructive azoospermia were excluded. Finally, only patients with idiopathic spermatogenesis disorder (normal clinical history, physical examination, and hormonal tests) were included in the study. All patients were subjected to cytogenetic analysis (karyotype). The data were analyzed using descriptive statistics and the independent t-test and chi-square test by SPSS version 20 software.
Results: The results showed that out of 135 patients studied, 73 patients (54%) had cytogenetic abnormalities, while no abnormalities were found in 62 (46%) patients. The comparison of men with cytogenetic abnormalities with those without abnormalities showed statistically significant differences in terms of age, duration of infertility, and spouse’s age (P=0.001). In patients carrying cytogenetic abnormalities, 33 (45%) patients had sex chromosome problems (the most common defect was 46, XY, del (Y) (q11.2- qter)) while 40 (55%) patients revealed abnormalities in autosomal chromosomes (the most common autosomal chromosomal defect was 46, XY, inv (1) (p22q24)). Oligoasthenoteratozoospermia (OAT) was the most common spermatogenesis disorder in patients carrying cytogenetic abnormalities (n=15, 20%), followed by non-obstructive azoospermia (NOA) (n=12, 16%). Overall, deletions constituted the most frequent cytogenetic defects observed in those carrying abnormal karyotypes (n=30, 41%).
Conclusion: Considering the high incidence of chromosomal abnormalities in infertile men with OAT and NOA, it is strongly suggested to conduct cytogenetic analysis in these patients to detect microdeletions in chromosome Y before administering assisted-reproductive technology techniques.

Keywords

Main Subjects

References
  1. Therman E, Susman M. Human Chromosomes: Structure, Behavior, And Effects. Springer Science & Business Media; 2012. doi: 10.1007/978-1-4684-0107-3.
  2. Leslie SW, Soon-Sutton TL, Khan MA. Male infertility. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024.
  3. Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod Biomed Online. 2007;14(6):734-45. doi: 10.1016/s1472- 6483(10)60677-3.
  4. Duvuru R, Halabi M, Omolaoye TS, Du Plessis SS. The genetic causes of male infertility: a Middle East and North Africa perspective. F1000Res. 2022;11:125. doi: 10.12688/ f1000research.106950.2.
  5. Carrell DT, De Jonge C, Lamb DJ. The genetics of male infertility: a field of study whose time is now. Arch Androl. 2006;52(4):269-74. doi: 10.1080/01485010500503603.
  6. Eisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K, et al. Male infertility. Nat Rev Dis Primers. 2023;9(1):49. doi: 10.1038/s41572-023-00459-w.
  7. Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007;92(3):762-70. doi: 10.1210/ jc.2006-1981.
  8. Emery BR, Carrell DT. The effect of epigenetic sperm abnormalities on early embryogenesis. Asian J Androl. 2006;8(2):131-42. doi: 10.1111/j.1745-7262.2006.00127.x.
  9. Carrell DT. Contributions of spermatozoa to embryogenesis: assays to evaluate their genetic and epigenetic fitness. Reprod Biomed Online. 2008;16(4):474-84. doi: 10.1016/s1472- 6483(10)60454-3.
  10. Mateizel I, Verheyen G, Van Assche E, Tournaye H, Liebaers I, Van Steirteghem A. FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from azoospermic patients. Hum Reprod. 2002;17(9):2249-57. doi: 10.1093/ humrep/17.9.2249.
  11. Puzuka A, Alksere B, Gailite L, Erenpreiss J. Idiopathic infertility as a feature of genome instability. Life (Basel). 2021;11(7):628. doi: 10.3390/life11070628.
  12. Palermo GD, Colombero LT, Hariprashad JJ, Schlegel PN, Rosenwaks Z. Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI. Hum Reprod. 2002;17(3):570-5. doi: 10.1093/humrep/17.3.570.
  13. Singhal P, Pendkur G, Parihar RS, Singh S, Chakrabarty BK, Raghavendra SK. The spectrum of chromosomal abnormalities and endocrine profile of male infertility with nonobstructive semen abnormality: a case-control study. J Hum Reprod Sci. 2021;14(2):175-83. doi: 10.4103/jhrs.jhrs_165_20.
  14. Gianaroli L, Magli MC, Ferraretti AP, Munné S, Balicchia B, Escudero T, et al. Possible interchromosomal effect in embryos generated by gametes from translocation carriers. Hum Reprod. 2002;17(12):3201-7. doi: 10.1093/humrep/17.12.3201.
  15. Kuroda S, Usui K, Sanjo H, Takeshima T, Kawahara T, Uemura H, et al. Genetic disorders and male infertility. Reprod Med Biol. 2020;19(4):314-22. doi: 10.1002/rmb2.12336.
  16. Chandley AC, Edmond P, Christie S, Gowans L, Fletcher J, Frackiewicz A, et al. Cytogenetics and infertility in man. I. Karyotype and seminal analysis: results of a five-year survey of men attending a subfertility clinic. Ann Hum Genet. 1975;39(2):231-54. doi: 10.1111/j.1469-1809.1975. tb00126.x.
  17. Elliott DJ, Cooke HJ. The molecular genetics of male infertility. Bioessays. 1997;19(9):801-9. doi: 10.1002/bies.950190910.
  18. Krausz C, Forti G, McElreavey K. The Y chromosome and male fertility and infertility. Int J Androl. 2003;26(2):70-5. doi: 10.1046/j.1365-2605.2003.00402.x.
  19. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003;423(6942):825-37. doi: 10.1038/nature01722.
  20. Poot M, Hochstenbach R. Prevalence and phenotypic impact of robertsonian translocations. Mol Syndromol. 2021;12(1):1- 11. doi: 10.1159/000512676.
  21. Vogt PH. Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online. 2005;10(1):81-93. doi: 10.1016/s1472-6483(10)60807-3.
  22. Witherspoon L, Dergham A, Flannigan R. Y-microdeletions: a review of the genetic basis for this common cause of male infertility. Transl Androl Urol. 2021;10(3):1383-90. doi: 10.21037/tau-19-599.
  23. Guarducci E, Nuti F, Becherini L, Rotondi M, Balercia G, Forti G, et al. Estrogen receptor alpha promoter polymorphism: stronger estrogen action is coupled with lower sperm count. Hum Reprod. 2006;21(4):994-1001. doi: 10.1093/humrep/dei439.
  24. Reynolds N, Cooke HJ. Role of the DAZ genes in male fertility. Reprod Biomed Online. 2005;10(1):72-80. doi: 10.1016/ s1472-6483(10)60806-1.
  25. Schnieders F, Dörk T, Arnemann J, Vogel T, Werner M, Schmidtke J. Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum Mol Genet. 1996;5(11):1801-7. doi: 10.1093/hmg/5.11.1801.
  26. Mahasneh IA, Abdul Rahim FE, Ennaji MM, Abumsimir B, Kasmi Y. Diagnostic screening of the microdeleation mutations in the azoospermia factor-gene cluster of the Y chromosome and; prostate cancer among Arabs: toward establishment of gene therapy platform in the region. In: Ennaji MM, ed. Immunological Implications and Molecular Diagnostics of Genitourinary Cancer. Academic Press; 2023. p. 115-39. doi: 10.1016/b978-0-323-85496-2.00008-7.
  27. Nuti F, Krausz C. Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod Biomed Online. 2008;16(4):504-13. doi: 10.1016/s1472-6483(10)60457-9.
  28. Krausz C, Rosta V, Swerdloff RS, Wang C. Genetics of male infertility. In: Pyeritz RE, Korf BR, Grody WW, eds. Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics. 7th ed. Academic Press; 2022. p. 121-47. doi: 10.1016/b978-0-12-815236-2.00010-2.
  29. De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, Devos A, et al. A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci U S A. 2004;101(5):1327-32. doi: 10.1073/pnas.0308114100.
  30. Zhang M, Fan HT, Zhang QS, Wang XY, Yang X, Tian WJ, et al. Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin province, China. Genet Mol Res. 2015;14(4):16178-84. doi: 10.4238/2015. December.8.7.
  1. Mierla D, Jardan D, Stoian V. Chromosomal abnormality in men with impaired spermatogenesis. Int J Fertil Steril. 2014;8(1):35-42.
  2. Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, et al. Cytogenetics of infertile men. Hum Reprod. 1996;11 Suppl 4:1-26. doi: 10.1093/humrep/11.suppl_4.1.
  3. Zhou-Cun A, Yang Y, Zhang SZ, Zhang W, Lin L. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia. Yi Chuan Xue Bao. 2006;33(2):111-6. doi: 10.1016/s0379- 4172(06)60029-2.
  4. Rabani SM, Moosavizadeh A. A study on causes of azoospermia in urology clinic of Yasuj University of Medical Sciences. Armaghane Danesh. 2006 Oct 10;11(3):81-7. [Persian].
  5. Kalantari P, Sepehri H, Akbari MT, Osati Ashtiani Z, Behjati F. Chromosomal anomalies in infertile azoospermic and oligospermic men. Tehran Univ Med J. 2001;59(3):60-71. [Persian].
  6. Fu L, Xiong DK, Ding XP, Li C, Zhang LY, Ding M, et al. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men. J Assist Reprod Genet. 2012;29(6):521-7. doi: 10.1007/s10815-012-9741-y.
  7. Pylyp LY, Spinenko LO, Verhoglyad NV, Zukin VD. Chromosomal abnormalities in patients with oligozoospermia and non-obstructive azoospermia. J Assist Reprod Genet. 2013;30(5):729-32. doi: 10.1007/s10815-013-9990-4.
  8. Arafa MM, Majzoub A, AlSaid SS, El Ansari W, Al Ansari A, Elbardisi Y, et al. Chromosomal abnormalities in infertile men with azoospermia and severe oligozoospermia in Qatar and their association with sperm retrieval intracytoplasmic sperm injection outcomes. Arab J Urol. 2018;16(1):132-9. doi: 10.1016/j.aju.2017.11.009.
  9. Nagvenkar P, Desai K, Hinduja I, Zaveri K. Chromosomal studies in infertile men with oligozoospermia & non-obstructive azoospermia. Indian J Med Res. 2005;122(1):34-42.
  10. Önalan Etem E, Yüce H, Erol D, Deveci ŞD, Ceylan GG, Elyas H. Original research cytogenetic analysis in infertile males with sperm anomalies. Marmara Med J. 2009;22(3):217-56.
  11. Evans JA, Canning N, Hunter AG, Martsolf JT, Ray M, Thompson DR, et al. A cytogenetic survey of 14,069 newborn infants. III. an analysis of the significance and cytologic behavior of the Robertsonian and reciprocal translocations. Cytogenet Cell Genet. 1978;20(1-6):96-123. doi: 10.1159/000130843.
  12. Pandiyan N, Jequier AM. Mitotic chromosomal anomalies among 1210 infertile men. Hum Reprod. 1996;11(12):2604- 8. doi: 10.1093/oxfordjournals.humrep.a019178.
  13. Najmabadi H, Huang V, Yen P, Subbarao MN, Bhasin D, Banaag L, et al. Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a sequence-tagged site-based mapping strategy. J Clin Endocrinol Metab. 1996;81(4):1347-52. doi: 10.1210/jcem.81.4.8636331.
  14. Qureshi SJ, Ross AR, Ma K, Cooke HJ, Intyre MA, Chandley AC, et al. Polymerase chain reaction screening for Y chromosome microdeletions: a first step towards the diagnosis of genetically-determined spermatogenic failure in men. Mol Hum Reprod. 1996;2(10):775-9. doi: 10.1093/molehr/2.10.775.
  15. Reijo R, Alagappan RK, Patrizio P, Page DC. Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. Obstet Gynecol Surv. 1996;51(11):675- 6. doi: 10.1097/00006254-199611000-00020.
  16. Foresta C, Ferlin A, Garolla A, Rossato M, Barbaux S, De Bortoli A. Y-chromosome deletions in idiopathic severe testiculopathies. J Clin Endocrinol Metab. 1997;82(4):1075- 80. doi: 10.1210/jcem.82.4.3798.
  17. Foresta C, Ferlin A, Garolla A, Moro E, Pistorello M, Barbaux S, et al. High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell-only syndrome. Hum Reprod. 1998;13(2):302-7. doi: 10.1093/humrep/13.2.302.
  18. Pryor JL, Kent-First M, Muallem A, Van Bergen AH, Nolten WE, Meisner L, et al. Microdeletions in the Y chromosome of infertile men. J Urol. 1998;159(2S):608-9. doi: 10.1016/ s0022-5347(01)63889-8.
  19. Simoni M. Molecular diagnosis of Y chromosome microdeletions in Europe: state-of-the-art and quality control. Hum Reprod. 2001;16(3):402-9. doi: 10.1093/ humrep/16.3.402.
  20. Clementini E, Palka C, Iezzi I, Stuppia L, Guanciali-Franchi P, Tiboni GM. Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques. Hum Reprod. 2005;20(2):437-42. doi: 10.1093/ humrep/deh626.
Journal of Kerman University of Medical Sciences
Volume 32
Pages 1-7
Files
Share
How to cite
Statistics