Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Expression of Synaptonemal Complex Protein 3 (SYCP3) mRNA in the testis: a molecular marker for spermatogenesis in azoospermic men

Authors
Mahmood Aarabi 1
Haleh Soltanghoraee 2
Mohsen Aarabi 3
Reza Behjati Ardakani 1
Naser Amirjannati 2
Maerefat Ghaffari 2
Mohammad Reza Sadeghi 2
Mohammad Hossein Modarresi 4
1 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
2 Avicenna Infertility Clinic, Avicenna Research Institute (ACECR), Tehran, Iran; Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
3 Academic Unit of clinical Pharmacology ,University of Sheffield, Sheffield, United Kingdom
4 Avicenna Infertility Clinic, Avicenna Research Institute (ACECR), Tehran, Iran; Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Department of Medical Genetics, Faculty of Medicine, Teh
Abstract
Introduction: Men with unexplained infertility and azoospermia are often observed in the context of genetic defects. The expression of a wide variety of genes is developmentally regulated during human meiosis. Synaptonemal Protein 3 (SYCP3) gene, located on chromosome 12, encodes a DNA-binding protein as the structural component of the synaptonemal complex,which mediates the synopsis or homologous pairing of chromosomes during meiosis. Absence of SYCP3 in mice may lead to male infertility as well as female sub-fertility. SYCP3 expression analysis could be a tool for the prediction of human spermatogenesis progression, especially in infertile men. Materials & Methods: SYCP3 mRNA expression in testicular samples of 110 patients with non-obstructive azoospermia were studied in Avesina Infertility Clinic in Tehran, Iran during 2005 and early 2006. Semi-quantitative nested reverse transcriptase-PCR was employed in order to find the strength of gene expression. Using histopathological scoring for all samples, the expression level of SYCP3 during spermatogenesis was also evaluated. Results: Testicular SYCP3 mRNA expression was observed in 67 patients (60.9%). The expression level correlated with the degree of spermatogenic failure (p < 0.0001). While this gene had been expressed in patients with hypo-spermatogenesis and maturation arrest, a lack of expression was seen in those with spermatogonial arrest, Sertoli cell-only syndrome and testicular atrophy. Conclusion: These data indicate that SYCP3 is expressed in the human testis and it is restricted to germ cells. Our findings, in association with those obtained in experimental animals, show that lack of SYCP3 expression may have negative effects on spermatogenesis and male fertility. SYCP3 gene expression may help detect specific spermatogenesis stages in conjunction with histopathological findings.
Keywords
Azoospermia
Male infertility
spermatogenesis
Synaptonemal complex protein 3
Testicular biopsy
  1. Yuan L., Liu J.G., Zhao J., Brundell E., Daneholt B. Hoog C. The murine SCP3 gene is required for synap tonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell.2000;5(1):73-83.
  2. Dym M. Spermatogonial stem cells of the testis. Proc Natl Acad Sci USA.1994;91(24):11287-9.
  3. Foley G.L., Overview of male reproductive pathology.Toxicol Pathol.2001;29(1):49-63.
  4. Parra M.T., Viera A., Gomez R., Page J., Benavente R., Santos J.L., et al., Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetocho-res during mouse meiosis I. J Cell Sci.2004;117(Pt7): 1221-34.
  5. Eijpe M., Offenberg H., Goedecke W., Heyting C. Lo-calisation of RAD50 and MRE11 in spermatocyte nuc-lei of mouse and rat. Chromosoma.2000;109(1-2):123-32.
  6. Meuwissen R.L., Offenberg H.H., Dietrich A.J., Riese-wijk A., Van Iersel M. Heyting C. A coiled-coil related protein specific for synapsed regions of meiotic pro-phase chromosomes. Embo J.1992;11(13):5091-100.
  7. Dobson M.J., Pearlman R.E., Karaiskakis A., Spyro-poulos B., Moens P.B.Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunc-tion. J Cell Sci.1994;107(Pt 10):2749-60.
  8. Lammers J.H., Offenberg H.H., Van Aalderen M., Vink A.C., Dietrich A.J., Heyting C. The gene encoding a major component of the lateral elements of synapto-nemal complexes of the rat is related to X-linked lymphocyte-regulated genes. Mol Cell Biol.1994;14 (2):1137-46.
  9. Offenberg H.H., Schalk J.A., Meuwissen R.L., Van Aalderen M., Kester H.A., Dietrich A.J., et al., SCP2: a major protein component of the axial elements of synaptonemal complexes of the rat. Nucleic Acids Res. 1998;26(11):2572-9.
  10. Yuan L., Pelttari J., Brundell E., Bjorkroth B., Zhao J., Liu J.G., et al. The synaptonemal complex protein SCP3 can form multistranded, cross-striated fibers in vivo. J Cell Biol.1998;142(2):331-9.
  11. Liebe B., Alsheimer M., Hoog C., Benavente R., Scherthan H. Telomere attachment, meiotic chromo-some condensation, pairing, and bouquet stage duration are modified in spermatocytes lacking axial elements. Mol Biol Cell.2004;15(2):827-37.
  12. Wang P., McCarrey J.R., Yang F., Page D.C. An abundance of X-linked genes expressed in spermato-gonia. Nat Genet.2001;27(4):422-26.
  13. Yuan L., Liu J.G., Hoja M.R., Wilbertz J., Nordqvist K., Hoog C. Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SCP3. Science.2002;296(5570):1115-8.
  14. Matzuk M.M., Lamb D.J. Genetic dissection of mam-malian fertility pathways. Nat Cell Biol.2002;(4Suppl): 41-9.
  15. Seshagiri P.B. Molecular insights into the causes of male infertility. J Biosci.2001;26(4 Suppl):429-35.
  16. Judis L., Chan E.R., Schwartz S., Seftel A., Hassold T. Meiosis I arrest and azoospermia in an infertile male explained by failure of formation of a component of the synaptonemal complex. Fertil Steril.2004;81(1): 205-9.
  17. Miyamoto T., Hasuike S., Yogev L., Maduro M.R., Ishikawa M., Westphal H., et al. Azoospermia in pa-tients heterozygous for a mutation in SYCP3. Lancet. 2003;362(9397):1714-9.
  18. Niemeyer P., Tureci O., Eberle T., Graf N., Pfreund-schuh M., Sahin U. Expression of serologically identi-fied tumor antigens in acute leukemias. Leuk Res. 2003;27(7):655-60.
  19. Holstein A.F., Schulze W., Davidoff M. Understan-ding spermatogenesis is a prerequisite for treatment. Reprod Biol Endocrinol.2003;1:107.
  20. Handelsman D.J., Spaliviero J.A., Simpson J.M., Allan C.M., Singh J., Spermatogenesis without gona-dotropins: maintenance has a lower testosterone threshold than initiation. Endocrinology.1999;140(9): 3938-46.
  21. Walker W.H., Cheng J. FSH and testosterone signa-ling in Sertoli cells. Reproduction.2005;130(1): 15-28.
  22. Silva F.R., Leite L.D., Wassermann G.F., Rapid signal transduction in Sertoli cells. Eur J Endocrinol.2002; 147(3):425-33.
  23. Steger K., Rey R., Louis F., Kliesch S., Behre H.M., Nieschlag E., et al. Reversion of the differentiated phenotype and maturation block in Sertoli cells in pathological human testis. Hum Reprod.1999;14(1): 136-43.
  24. De Gendt K., Swinnen J.V., Saunders P.T., Schoon-jans 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 USA.2004;101(5):1327-32.
  25. Anawalt B.D., Bebb R.A., Matsumoto A.M., Groome N.P., Illingworth P.J., McNeilly A.S., et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J Clin Endo-crinol Metab.1996;81(9):3341-5.
  26. Sokol R.Z., Swerdloff R.S., Endocrine Evaluation, in L. Lipshultz and S. Howards, Editors. Infertility in the Male: Mosby.1997;p:210-218.
  27. Schrader M., Muller M., Schulze W., Heicappell R., Krause H., Straub B., et al. Quantification of the expre-ssion level of the gene encoding the catalytic subunit of telomerase in testicular tissue specimens predicts successful sperm recovery. Hum Reprod.2002;17(1): 150-6.
  28. Weikert S., Schrader M., Muller M., Schulze W., Krause H., Miller K. Expression levels of the inhibitor of apoptosis survivin in testes of patients with normal spermatogenesis and spermatogenic failure. Fertil Steril.2005;83 (Suppl 1):1100-5.
  29. Song G.J., Lee H., Park Y., Lee H.J., Lee Y.S., Seo J.T., et al. Expression pattern of germ cell-specific genes in the testis of patients with nonobstructive azoo-spermia: usefulness as a molecular marker to predict the presence of testicular sperm. Fertil Steril.2000;73 (6):1104-8.
Journal of Reproduction & Infertility
Volume 6, Issue 5
Winter 2006
Pages 495-504