International Journal of Infertility & Fetal Medicine

Register      Login

VOLUME 15 , ISSUE 1 ( January-April, 2024 ) > List of Articles


Role of Genetics in Human Infertility

Ronak V Manikawala, Jigna Desai

Keywords : Azoospermia factor microdeletions, Infertility, Karyotyping

Citation Information : Manikawala RV, Desai J. Role of Genetics in Human Infertility. Int J Infertil Fetal Med 2024; 15 (1):6-14.

DOI: 10.5005/jp-journals-10016-1329

License: CC BY-NC 4.0

Published Online: 29-02-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Aim: To study the role of genetics in human infertility. Materials and methods: We collected 60 male and 41 female blood samples from infertile couples and carried out a cytogenetic study in both males and females, whereas molecular study was done in only male subjects. Standard Giemsa banding karyotyping protocol was followed for the cytogenetic study. For azoospermia factor (AZF) microdeletion studies, deoxyribonucleic acid (DNA) isolation was followed by multiplex polymerase chain reaction (PCR) using AZF-specific sequence tagged site (STS) markers. Results: In the female cytogenetic study, no structural or chromosomal abnormalities were found; three (7.31%) had polymorphic variants. In males, one (1.6%) had autosomal structural 46, XY, t (3; 17) (p25; q22), one (1.6%) had sex chromosomal numerical abnormalities 47, XXY (12)/46, XX (8) and four (6.66%) had the polymorphic variant. Two males and two females had 9qh+ with other normal chromosomal constitutions. In the same way, two other types of polymorphism were also observed, that is, 21pS+ in one male and one female, whereas 22pS+ was observed in one male subject. The translocation 46, XY, t (3; 17) (p25; q22) we have found is unique. In male blood samples, we studied six gene mutations named AZFa (sy84), AZFa (sy86), AZFb (sy127), AZFb (sy134), AZFc (sy254), and AZFc (sy255). We have observed deletions in eight subjects with a microdeletion frequency of 13.33%, where seven (87.5%) were azoospermic, and one (12.5%) was oligozoospermic. Most found microdeletions were AZFb (sy127) in three males and AZFb (sy134) in three males. AZFa (sy86) and AZFa (sy254) deletions were found in one male. Conclusion: As per our knowledge, there is one novel translocation 46, XY, t (3; 17) (p25; q22) in one male patient from our research. We have also found AZF microdeletions in oligozoospermic and azoospermic patients. The results indicate the importance of karyotyping and microdeletion screening in chromosome Y for infertile couples before advising them of costlier treatments. Clinical significance: The present investigation is a valuable consideration for prognosis, which can be helpful for counseling couples and minimizing the potential risk of transmission of genetic abnormalities to future generations.

PDF Share
  1. Dechanet C, Anahory T, Mathieu Daude JC, et al. Effects of cigarette smoking on reproduction. Hum Reprod Update 2011;17(1):76–95. DOI: 10.1093/humupd/dmq033
  2. Natarajamani S, Janani D, Subramanian M, et al. Correlation of semen PH with other semen parameters in a sub fertile male population attending a tertiary ART center in South India. Int J Sci Res Pub 2014;4(8):355–359.
  3. Vogt PH. Molecular basis of male infertility. Int J Androl 1997 20(Suppl 3):2–10. PMID: 9466180.
  4. Onrat ST, Söylemez Z, Elmas M. 46, XX, der (15), t (Y; 15)(q12; p11) karyotype in an azoospermic male. Indian J Hum Genet 2012;18(2):241–245. DOI: 10.4103/0971-6866.100785
  5. Foresta C, Ferlin A, Garolla A, et al. High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell-only syndrome. Hum Reprod 1998;13(2):302–307. DOI: 10.1093/humrep/13.2.302
  6. Vogt P, Chandley AC, Hargreave TB, et al. Microdeletions in interval 6 of the Y chromosome of males with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene. Hum Genet 1992;89(5):491–496. DOI: 10.1007/BF00219172
  7. Krausz C, McElreavey K. Y chromosome and male infertility. Front Biosci 1999;4:E1–E8. DOI: 10.2741/krausz
  8. Hungerford DA. Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Technol 1965;40(6):333–338. DOI: 10.3109/10520296509116440
  9. Seabright M. A rapid banding technique for human chromosomes. Lancet 1971;2(7731):971–972. DOI: 10.1016/s0140-6736(71)90287-x
  10. Lázaro-Silva DN, De Mattos JCP, Castro H, et al. The use of DNA extraction for molecular biology and biotechnology training: a practical and alternative approach. Creat Educ 2015;6(8):762–772. DOI: 10.4236/ce.2015.68079
  11. Foresta C, Ferlin A, Gianaroli L, et al. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet 2002;10(5): 303–312. DOI: 10.1038/sj.ejhg.5200805
  12. Baird DT, Collins J, Egozcue J, et al. Fertility and ageing. Hum Reprod Update 2005;11(3):261–276. DOI: 10.1093/humupd/dmi006
  13. Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet 1964;16(1):1–25. PMID: 14131871.
  14. Vicdan A, Vicdan K, Günalp S, et al. Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility. Eur J Obstet Gynecol Reprod Biol 2004;117(1):49–54. DOI: 10.1016/j.ejogrb.2003.07.006
  15. Turan GA, Kaya I, Genç M, et al. Chromosomal abnormalities and polymorphisms among couples with recurrent in vitro fertilization (IVF) failure. Sifa Med J 2015;2(3):49. DOI: 10.4103/2148-7731.166854
  16. Zhang HG, Wang RX, Li LL, et al. Male carriers of balanced reciprocal translocations in Northeast China: sperm count, reproductive performance, and genetic counseling. Genet Mol Res 2015;14(4):18792–18798. DOI: 10.4238/2015
  17. Verma RS. Heterochromatin: Molecular and Structural Aspects. Cambridge University Press; 1988.
  18. Ferlin A, Arredi B, Speltra E, 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):762–770. DOI: 10.1210/jc.2006-1981
  19. Krausz C, Forti G, McElreavey K. The Y chromosome and male fertility and infertility 1. Int J androl 2003;26(2):70–75. DOI: 10.1046/j.1365-2605.2003.00402.x
  20. Hellani A, Al-Hassan S, Iqbal MA, et al. Y chromosome microdeletions in infertile men with idiopathic oligo-or azoospermia. J Exp Clin Assist Reprod 2006;3(1):1–6. DOI: 10.1186/1743-1050-3-1
  21. Kamp C, Hirschmann P, Voss H, et al. Two long homologous retroviral sequence blocks in proximal Yq11 cause AZFa microdeletions as a result of intrachromosomal recombination events. Hum Mol Genet 2000;9(17):2563–2572. DOI: 10.1093/hmg/9.17.2563
  22. Girardi SK, Mielnik A, Schlegel PN. Submicroscopic deletions in the Y chromosome of infertile men. Hum Reprod 1997;12(8):1635–1641. DOI: 10.1093/humrep/12.8.1635
  23. Krausz C, Quintana-Murci L, McElreavey K. Prognostic value of Y deletion analysis: what is the clinical prognostic value of Y chromosome microdeletion analysis? Hum Reprod 2000;15(7): 1431–1434. DOI: 10.1093/humrep/15.7.1431
  24. Ferlin A, Moro E, Rossi A, et al. The human Y chromosome's azoospermia factor b (AZFb) region: sequence, structure, and deletion analysis in infertile men. J Med Genet 2003;40(1):18–24. DOI: 10.1136/jmg.40.1.18
  25. Kuroda-Kawaguchi T, Skaletsky H, Brown LG, et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 2001;29(3):279–286. DOI: 10.1038/ng757
  26. Hopps CV, Mielnik A, Goldstein M, et al. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Reprod 2003;18(8):1660–1665. DOI: 10.1093/humrep/deg348
  27. Mafra FA, Christofolini DM, Bianco B, et al. Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service. Int Braz J Urol 2011;37(2):244–250. DOI: 10.1590/s1677-55382011000200011
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.