Polymorphism of the testis-specific serine/threonine kinase 2 gene and risk of asthenozoospermia in Côte d'Ivoire
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20191923Keywords:
Asthenozoospermia, Human spermatozoa, Gene mutation, Male infertility, TSSK2 polymorphismAbstract
Background: The testis-specific serine/threonine protein kinase (TSSK2) is an indispensable protein responsible for the mobility of spermatozoa expressed specifically in the germ cells during spermatogenesis and present in the mature spermatozoa. Its gene mutation could constitute a risk of infertility. The aim of this study is to investigate the polymorphism of this TSSK2 gene in men with asthenozoospermia.
Methods: The ejaculates were obtained from patients attending the reproductive biology unit of Institut Pasteur of Côte d’Ivoire for their spermiological evaluations. The semen analyses are performed with the automatic sperm analyzer SQA-Vision. 30 sperms, including 20 asthenozoosperms and 10 normosperms, were selected from their spermiological results and the spermatozoa DNA was extracted by the phenol/chloroform method. Direct Sequencing of the spermatozoa DNA fragments was done using the Sanger method. The frequencies of mutation were analysis with the Fisher and Mann-Whitney tests.
Results: It was revealed 17 mutations in 22 ejaculates. The frequent mutations are c.839C>T (T280M), c.816G>C (L372L), c.1026G>A (R342R), c.785A>C (H262P) and c.80A>G (K27R) with respectively frequencies of 50.0%, 26.67%, 16.67%, 13.33% and 10.0%. The analysis of these mutations indicated a significant difference in the frequency of occurrence of mutations between normosperms and asthenozoosperms (p-value = 0.01).
Conclusions: This study shows that mutations in the TSSK2 gene are more common in asthenozoosperm ejaculates than normosperm ejaculates. This fact suggests the probable association of mutations in the TSSK2 gene with asthenozoospermia.
References
Curi SM, Ariagno J, Chenlo P, Mendeluk G, Pugliese M, Sardi S, et al. Asthenozoospermia: analysis of a large population. Arch Androl. 2003;49:343-9.
Ikechebelu JI, Adinma JI, Orie EF, Ikegwuonu SO. High prevalence of male infertility in southeastern Nigeria. J Obstet Gynaecol. 2003;23:657-9.
Jihad D, Drissi M, Koutaini A, Rhrab B, Fehati D, El Hamzaoui S. Les facteurs influençant la fertilité masculine. IJISR. 2015;15:15-26.
Jules A, Konan N, Yapi Y, Founzégué C, Marie N, Gnogbo B, et al. The asthenozoospermia as a major sperm abnormality in males assessed for semen analysis in Institut Pasteur of Côte d’Ivoire. JAMSAT. 2018;4:7-12.
Krausz C, Escamilla R, Chianese C. Genetics of male infertility: from research to clinic. Reproduction. 2015;150:R159-74.
Massart A, Lissens W, Tournaye H, Stouffs K. Genetic causes of spermatogenic failure. Asian J Androl. 2012;14:40-8.
Tamowski S, Aston KI, Carrell D. The use of transgenic mouse models in the study of male infertility. Syst Biol Reprod Med. 2010;56:260-73.
Toshinobu M, Gaku M, Takeshi S, Hiroto U, Hiroshi O, Kazuo S. Human male infertility and its genetics causes. Reprod Med Biol. 2017;16:81-8.
Luconi M, Forti G, Baldi E. Pathophysiology of sperm motility. Front Biosci. 2006;11:1433-47.
Yunes R, Doncel G, Acosta A. Incidence of sperm-tail tyrosine phosphorylation and hyperactivated motility in normozoospermic and asthenozoospermic human sperm samples. Biocell. 2003;27:29-36.
Buffone MG, Calamera JC, Verstraeten SV, Doncel GF. Capacitation-associated protein tyrosine phosphorylation and membrane fluidity changes are impaired in the spermatozoa of asthenozoospermic patients. Reproduction. 2005;129:697-705.
Li Y, Sosnik J, Brassard L, Reese M, Spiridonov N, Bates T, et al. Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis. Mol Hum Reprod. 2011;17:42-56.
Shetty J, Sinvilleb R, Shumilinc I, Minorc W, Zhanga J, Hawkinsonb J, et al. Recombinant production of enzymatically active male contraceptive drug target hTSSK2 - Localization of the TSKS Domain Phosphorylated by TSSK2. Protein Expr Purif. 2016;121:88-96.
Bucko-Justyna M. Search for mutations in genes coding for TSSK1 and TSSK2 in patients with infertility. In: Testis specific serine-threonine kinases: regulation and their role in disease. University of Utrecht, NL. 2005:67-72.
Xu B, Hao Z, Jha K, Zhang Z, Urekar C, Digilio L, et al. Targeted deletion of Tssk1 and 2 causes male infertility due to haploinsufficiency. Dev Biol. 2008;319:211-22.
Zhang H, Su D, Yang Y, Zhang W, Liu Y, Bai G, et al. Some single-nucleotide polymorphisms of the TSSK2 gene may be associated with human spermatogenesis impairment. J Androl. 2010;31:388-92.
Xu B, Hao Z, Jha K, Digilio L, Urekar C, Kim Y, et al. Validation of a testis specific serine/threonine kinase [TSSK] family and the substrate of TSSK1 & 2, TSKS, as contraceptive targets. Soc Reprod Fertil Suppl. 2007;63:87-101.
Zhang Z, Kostetskii I, Tang W, Haig-Ladewig L, Sapiro R, Wei Z, et al. Deficiency of SPAG16L causes male infertility associated with impaired sperm motility. Biol Reprod. 2006;74:751-9.
Zhang Z, Shen X, Jones BH, Xu B, Herr J, Strauss JF. Phosphorylation of Mouse Sperm Axoneme Central Apparatus Protein SPAG16L by a Testis-Specific Kinase, TSSK2. Biol Reprod. 2008;79:75-83.
Masahito T, Yukihiro T, Haruo M, Takashi M, Nobuo Y, Kunihiro O. Dynamic changes in the cytoskeleton during human spermiogenesis. Fertil Steril. 2005;84:1241-8.
Hall T. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser. 1999;41:95-8.
World Health Organization (WHO). Laboratory manual for the examination and processing of human semen. WHO Library Cataloguing-in-Publication Data, CH. 5th edn. 2010.
Xu B, Hao Z, Jha K, Zhang Z, Urekar C, Digilio L, et al. TSKS concentrates in spermatid centrioles during flagellogenesis. Dev Biol. 2008;319:201-0.
