Clinical and Experimental Reproductive Medicine

  • 제50권4호
  • /
  • Pages.253-261
  • /
  • 2023
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Polymorphisms and expression levels of TNP2, SYCP3, and AZFa genes in patients with azoospermia

  • 투고 : 2023.05.27
  • 심사 : 2023.07.12
  • 발행 : 2023.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: Azoospermia (the total absence of sperm in the ejaculate) affects approximately 10% of infertile males. Despite diagnostic advances, azoospermia remains the most challenging issue associated with infertility treatment. Our study evaluated transition nuclear protein 2 (TNP2) and synaptonemal complex protein 3 (SYCP3) polymorphisms, azoospermia factor a (AZFa) microdeletion, and gene expression levels in 100 patients with azoospermia. Methods: We investigated a TNP2 single-nucleotide polymorphism through polymerase chain reaction (PCR) restriction fragment length polymorphism analysis using a particular endonuclease. An allele-specific PCR assay for SYCP3 was performed utilizing two forward primers and a common reverse primer in two PCR reactions. Based on the European Academy of Andrology guidelines, AZFa microdeletions were evaluated by multiplex PCR. TNP2, SYCP3, and the AZFa region main gene (DEAD-box helicase 3 and Y-linked [DDX3Y]) expression levels were assessed via quantitative PCR, and receiver operating characteristic curve analysis was used to determine the diagnostic capability of these genes. Results: The TNP2 genotyping and allelic frequency in infertile males did not differ significantly from fertile volunteers. In participants with azoospermia, the allelic frequency of the SYCP3 mutant allele (C allele) was significantly altered. Deletion of sY84 and sY86 was discovered in patients with azoospermia and oligozoospermia. Moreover, SYCP3 and DDX3Y showed decreased expression levels in the azoospermia group, and they exhibited potential as biomarkers for diagnosing azoospermia (area under the curve, 0.722 and 0.720, respectively). Conclusion: These results suggest that reduced SYCP3 and DDX3Y mRNA expression profiles in testicular tissue are associated with a higher likelihood of retrieving spermatozoa in individuals with azoospermia. The homozygous genotype TT of the SYCP3 polymorphism was significantly associated with azoospermia.

키워드

참고문헌

  1. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci 2015;8:191-6. https://doi.org/10.4103/0974-1208.170370
  2. Ghanami Gashti N, Sadighi Gilani MA, Jabari A, Qasemi M, Feizollahi N, Abbasi M. The germ cell-specific markers ZPBP2 and PGK2 in testicular biopsies can predict the presence as well as the quality of sperm in non-obstructive azoospermia patients. Reprod Sci 2021;28:1466-75. https://doi.org/10.1007/s43032-020-00427-9
  3. Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med 2021;10:3144.
  4. Lv MQ, Zhou L, Ge P, Li YX, Zhang J, Zhou DX. Over-expression of hsa_circ_0000116 in patients with non-obstructive azoospermia and its predictive value in testicular sperm retrieval. Andrology 2020;8:1834-43. https://doi.org/10.1111/andr.12874
  5. Kasak L, Laan M. Monogenic causes of non-obstructive azoospermia: challenges, established knowledge, limitations and perspectives. Hum Genet 2021;140:135-54. https://doi.org/10.1007/s00439-020-02112-y
  6. Ferlin A, Calogero AE, Krausz C, Lombardo F, Paoli D, Rago R, et al. Management of male factor infertility: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS): Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR). J Endocrinol Invest 2022;45:1085-113. https://doi.org/10.1007/s40618-022-01741-6
  7. Abdelaal NE, Tanga BM, Abdelgawad M, Allam S, Fathi M, Saadeldin IM, et al. Cellular therapy via spermatogonial stem cells for treating impaired spermatogenesis, non-obstructive azoospermia. Cells 2021;10:1779.
  8. Nagirnaja L, Morup N, Nielsen JE, Stakaitis R, Golubickaite I, Oud MS, et al. Variant PNLDC1, defective piRNA processing, and azoospermia. N Engl J Med 2021;385:707-19. https://doi.org/10.1056/NEJMoa2028973
  9. Zakaria M, Al-ibraheemi A, Senhaji W, Ennaji M, Louanjli N, Zarqaoui M, et al. Severe oligospermia treatment with testicular sperm using "ICSI". Annu Res Rev Biol 2022;37:37-44. https://doi.org/10.9734/arrb/2022/v37i630514
  10. AlMaghamsi T, Iqbal N, Al-Esaei NA, Mohammed M, Eddin KZ, Ghurab F, et al. Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility. Ann Saudi Med 2020;40:321-9. https://doi.org/10.5144/0256-4947.2020.321
  11. Amor H, Zeyad A, Hammadeh ME. Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. Andrologia 2021;53:e13964.
  12. Alrahel A, Movahedin M, Mazaheri Z, Amidi F. Study of TNP1, Tekt1, and Plzf genes expression during an in vitro three-dimensional neonatal male mice testis culture. Iran Biomed J 2018;22:258-63. https://doi.org/10.29252/ibj.22.4.258
  13. Sharma R, Agarwal A. Defective spermatogenesis and sperm DNA damage. In: Zini A, Agarwal A, editors. A clinician's guide to sperm DNA and chromatin damage. Springer; 2018. p. 229-61.
  14. Hao SL, Ni FD, Yang WX. The dynamics and regulation of chromatin remodeling during spermiogenesis. Gene 2019;706:201-10. https://doi.org/10.1016/j.gene.2019.05.027
  15. Dhulqarnain AO, Takzaree N, Hassanzadeh G, Solhjo S, Tooli H, Nejad MY, et al. Osteocacin favours the expression of synaptonemal complex protein 3 in azoospermic mouse model. J Contemp Med Sci 2019;5:28-34. https://doi.org/10.22317/jcms.v5i1.542
  16. Ahmed A, Azova M. Distribution of the T657C polymorphism of the SYCP3 gene among Russian women living in Central Russia. In: Aghajanian's reading. Peoples' Friendship University of Russia named after Patrice Lumumba; 2018. p.37-8.
  17. Amirian M, Azizi H, Hashemi Karoii D, Skutella T. VASA protein and gene expression analysis of human non-obstructive azoospermia and normal by immunohistochemistry, immunocytochemistry, and bioinformatics analysis. Sci Rep 2022;12:17259.
  18. Xi Q, Zhang Z, Wang R, Li L, Li L, Zhu H, et al. Obstetric and perinatal outcomes of intracytoplasmic sperm injection for infertile men with Y chromosome microdeletions. Medicine (Baltimore) 2019;98:e17407.
  19. Al-Ouqaili MTS, Al-Ani SK, Alaany R, Al-Qaisi MN. Detection of partial and/or complete Y chromosome microdeletions of azoospermia factor a (AZFa) sub-region in infertile Iraqi patients with azoospermia and severe oligozoospermia. J Clin Lab Anal 2022;36:e24272.
  20. Colaco S, Modi D. Consequences of Y chromosome microdeletions beyond male infertility. J Assist Reprod Genet 2019;36:1329-37. https://doi.org/10.1007/s10815-019-01492-z
  21. Stus VP, Padalko LI, Polion MY. AZF-deletion: one of the genetic causes of male infertility. Urologiya 2018;22:50-3. https://doi.org/10.26641/2307-5279.22.1.2018.128146
  22. Colaco S, Modi D. Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol 2018;16:14.
  23. Tang D, Liu W, Li G, He X, Zhang Z, Zhang X, et al. Normal fertility with deletion of sY84 and sY86 in AZFa region. Andrology 2020;8:332-6. https://doi.org/10.1111/andr.12692
  24. Benderradji H, Prasivoravong J, Marcelli F, Barbotin AL, Catteau-Jonard S, Marchetti C, et al. Contribution of serum anti-Mullerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men. Basic Clin Androl 2021;31:15.
  25. Cioppi F, Rosta V, Krausz C. Genetics of azoospermia. Int J Mol Sci 2021;22:3264.
  26. Amjad S, Mushtaq S, Rehman R, Zahid N, Munir A, Siddiqui PQ. Spermatozoa retrieval in azoospermia and expression profile of JMJD1A, TNP2, and PRM2 in a subset of the Karachi population. Andrology 2021;9:1934-42. https://doi.org/10.1111/andr.13076
  27. Arefnia M, Motovali-Bashi M, Javadirad SM, Norioun H. Overexpression of hsa-miR-30a-5p and non-obstructive azoospermia: a case-control study. Int J Reprod Biomed 2022;20:399-404.
  28. Heidari MM, Danafar A, Moezzi F, Khatami M, Talebi AR. The association between TNP2 gene polymorphisms and Iranian infertile men with varicocele: a case-control study. Int J Reprod Biomed 2019;17:557-66. https://doi.org/10.18502/ijrm.v17i8.4821
  29. Li Y, Liu WS, Yi J, Kong SB, Ding JC, Zhao YN, et al. The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis. Asian J Androl 2020;22:79-87. https://doi.org/10.4103/aja.aja_49_19
  30. Rybina A, Lokshin V, Karibayeva S, Abshekenova A, Askar E, Valiev R. P-373 T657C SYCP3 mutation increases the risk of recurrent miscarriage: a meta-analysis. Hum Reprod 2022;37(Supplement 1):deac107-351. https://doi.org/10.1093/humrep/deac107.351
  31. Atia T, Abbas M, Ahmed AF. Azoospermia factor microdeletion in infertile men with idiopathic severe oligozoospermia or non-obstructive azoospermia. Afr J Urol 2015;21:246-53. https://doi.org/10.1016/j.afju.2015.02.004
  32. Romo-Yanez J, Sevilla-Montoya R, Perez-Gonzalez E, Flores-Reyes J, Laresgoiti-Servitje E, Espino-Sosa S, et al. AZFa, AZFb, AZFc and gr/gr Y-chromosome microdeletions in azoospermic and severe oligozoospermic patients, analyzed from a neural network perspective. Cir Cir 2022;90:202-9.
  33. Ramathal C, Angulo B, Sukhwani M, Cui J, Durruthy-Durruthy J, Fang F, et al. DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs. Sci Rep 2015;5:15041.
  34. Hammood S, Al-Khafaji S, Al-Sallami A. Detection Y chromosome microdeletions among Iraq population in infertile patients with azoospermia and severe oligospermia. Int J Drug Deliv Technol 2019;9:7.