Sperm Differentiation from a Cytoskeletal Perspective with a Focus on the Microtubulome: A New Window into Unknown Aspects of Male Infertility

Document Type : Review Article

Authors

1 MSc, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

2 PhD Student of Reproductive Biology, Department of Anatomy, School of Medicine, Iran University of Medical Sciences and Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Assistant Professor, Department of Obstetrics and Gynecology, Mousavi Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

4 Assistant Professor, Reproductive Biotechnology Research Center, Avicenna Research Institute (ARI), ACECR, Tehran, Iran

5 MSc, Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

6 Associate Professor, Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

7 Professor, Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

Abstract

According to the World Health Organization, infertility refers to a couple's inability to conceive following at least one year of regular unprotected sexual intercourse. Male infertility accounts for about half of the various causes of couples' infertility. This review aimed to investigate the cellular and molecular differentiation of spermatozoa, focusing on the structure of the cytoskeleton, microtubules, actin filaments, motor, and non-motor proteins, to study the known genes associated with their formation and function, as well as the proteins involved in intracellular cargo transport, and ultimately investigate their essential role in maintaining sperm morphology and motility and subsequent male reproduction and infertility. The importance of microtubules in the critical processes of sperm production, transformation, maturation, and fertility of spermatozoa is such that the term "microtubule" has been recently used to denote the microtubule and all microtubule-related components in the sperm cell. The cellular process of sperm evolution and differentiation was discussed first, followed by a description of the cytoskeletal system of the acroframosome-acroplaxome-manchette axis, which is involved in acrosome formation and development, sperm head and flagellum shaping mechanisms, in response to the current and future demands of infertility researchers and clinicians in this emerging field of research. The significance of the aberrant function of different components of the sperm cytoskeleton in creating major disorders associated with male infertility was next inspected to clarify the ambiguous aspects of this complex process.

Keywords

References

  1. Tüttelmann F, Gromoll J, Kliesch S. Genetics of male infertility [in German]. Urologe A 2008; 47(12): 1561-2, 1564-7.
  2. Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker H, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16(3): 231-45.
  3. Russell LD, Ettlin RA, Hikim APS, Clegg ED. Histological and histopathological evaluation of the testis. Int J Androl 1993; 16(1): 83.
  4. Teves ME, Roldan ERS, Krapf D, Strauss III JF, Bhagat V, Sapao P. Sperm differentiation: the role of trafficking of proteins. Int J Mol Sci 2020; 21(10): 3702.
  5. Kaverina I, Straube A. Regulation of cell migration by dynamic microtubules. Semin Cell Dev Biol 2011; 22(9): 968-74.
  6. Watanabe T, Noritake J, Kaibuchi K. Regulation of microtubules in cell migration. T Trends Cell Biol 2005; 15(2): 76-83.
  7. Glotzer M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol 2009; 10(1): 9-20.
  8. Jumeau F, Chalmel F, Fernandez-Gomez FJ, Carpentier C, Obriot H, Tardivel M, et al. Defining the human sperm microtubulome: an integrated genomics approach. Biol Reprod 2017; 96(1): 93-106.
  9. Gunes S, Sengupta P, Henkel R, Alguraigari A, Sinigaglia MM, Kayal M, et al. Microtubular dysfunction and male infertility. World J Mens Health 2020; 38(1): 9-23.
  10. Linck RW, Chemes H, Albertini DF. The axoneme: the propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility. J Assist Reprod Genet 2016; 33(2): 141-56.
  11. Auger JJ. Spermatozoa and sperm structure. In: Flaws JA, Spencer TE, editorts. Encyclopedia of Reproduction. 2nd Amsterdam, The Netherlands: Elsevier; 2018. p. 62-7.
  12. Lehti MS, Sironen A. Formation and function of sperm tail structures in association with sperm motility defects. Biol Reprod 2017; 97(4): 522-36.
  13. Kanatsu-Shinohara M, Shinohara T. Spermatogonial stem cell self-renewal and development. Annu Rev Cell Dev Biol 2013; 29: 163-87.
  14. Phillips BT, Gassei K, Orwig KE. Spermatogonial stem cell regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010; 365(1546): 1663-78.
  15. Nakano T, Nakata H, Kadomoto S, Iwamoto H, Yaegashi H, Iijima M, et al. Three-dimensional morphological analysis of spermatogenesis in aged mouse testes. Sci Rep 2021; 11(1): 23007.
  16. Malo AF, Gomendio M, Garde J, Lang-Lenton B, Soler AJ, Roldan ER. Sperm design and sperm function. Biol Lett 2006; 2(2): 246-9.
  17. Tourmente M, Gomendio M, Roldan ER. Sperm competition and the evolution of sperm design in mammals. BMC Evol Biol 2011; 11(1): 12.
  18. Firman RC, Garcia-Gonzalez F, Simmons LW, André GI. A competitive environment influences sperm production, but not testes tissue composition, in
    house mice. J Evol Biol 2018; 31(11): 1647-54.
  19. Kierszenbaum AL, Rivkin E, Tres LL. The actin-based motor myosin Va is a component of the acroplaxome, an acrosome-nuclear envelope junctional plate, and of manchette-associated vesicles. Cytogenet Genome Res 2003; 103(3-4): 337-44.
  20. Wei YL, Yang WX. The acroframosome-acroplaxome-manchette axis may function in sperm head shaping and male fertility. Gene 2018; 660: 28-40.
  21. Lie PP, Mruk DD, Lee WM, Cheng CY. Cytoskeletal dynamics and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010; 365(1546): 1581-92.
  22. Kierszenbaum AL, Rivkin E, Tres LL. Acroplaxome, an F-actin-keratin-containing plate, anchors the acrosome to the nucleus during shaping of the spermatid head. Mol Biol Cell 2003; 14(11): 4628-40.
  23. Funaki T, Kon S, Tanabe K, Natsume W, Sato S, Shimizu T, et al. The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis. Mol Biol Cell 2013; 24(17): 2633-44.
  24. Xiao N, Kam C, Shen C, Jin W, Wang J, Lee KM, et al. PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. J Clin Invest 2009; 119(4): 802-12.
  25. Tardif S, Guyonnet B, Cormier N, Cornwall GA. Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice. Mol Hum Reprod 2012; 18(6): 298-307.
  26. Kang-Decker N, Mantchev GT, Juneja SC, McNiven MA, van Deursen JM. Lack of acrosome formation in Hrb-deficient mice. Science 2001; 294(5546): 1531-3.
  27. Kierszenbaum AL, Tres LL. The acrosome-acroplaxome-manchette complex and the shaping of the spermatid head. Arch Histol Cytol 2004; 67(4): 271-84.
  28. Khawar MB, Gao H, Li W. Mechanism of acrosome biogenesis in mammals. Front Cell Dev Biol 2019;
    7: 195.
  29. Hardy DM, Oda M, Friend DS, Huang Jr T. A mechanism for differential release of acrosomal enzymes during the acrosome reaction. Biochem J 1991; 275(3): 759-66.
  30. Hou CC, Yang WX. Acroframosome-dependent KIFC1 facilitates acrosome formation during spermatogenesis in the caridean shrimp Exopalaemon modestus. PLoS One 2013; 8(9): e76065.
  31. Li Z, Pan CY, Zheng BH, Xiang L, Yang WX. Immunocytochemical studies on the acroframosome during spermiogenesis of the caridean shrimp Macrobrachium nipponense (Crustacea, Natantia). Invertebr Reprod Dev 2010; 54(3): 121-31.
  32. Kierszenbaum AL, Tres LL, Rivkin E, Kang-Decker N, Van Deursen JM. The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b-containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids. Biol Reprod 2004; 70(5): 1400-10.
  33. Russell LD, Weber JE, Vogl AW. Characterization of filaments within the subacrosomal space of rat spermatids during spermiogenesis. Tissue Cell 1986; 18(6): 887-98.
  34. Hayasaka S, Terada Y, Suzuki K, Murakawa H, Tachibana I, Sankai T, et al. Intramanchette transport during primate spermiogenesis: expression of dynein, myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis. Asian J Androl 2008; 10(4): 561-8.
  35. De Vries M, Ramos L, Housein Z, De Boer P. Chromatin remodelling initiation during human spermiogenesis. Biology Open 2012; 1(5): 446-57.
  36. Göb E, Schmitt J, Benavente R, Alsheimer M. Mammalian sperm head formation involves different polarization of two novel LINC complexes. PloS One 2010; 5(8): e12072.
  37. Tavalaee M, Nomikos M, Lai FA, Nasr-Esfahani MH. Expression of sperm PLCζ and clinical outcomes of ICSI-AOA in men affected by globozoospermia due to DPY19L2 deletion. Reprod Biomed Online 2018; 36(3): 348-55.
  38. Kierszenbaum AL, Rivkin E, Talmor-Cohen A, Shalgi R, Tres LL. Expression of full-length and truncated Fyn tyrosine kinase transcripts and encoded proteins during spermatogenesis and localization during acrosome biogenesis and fertilization. Mol Reprod Dev 2009; 76(9): 832-43.
  39. Kierszenbaum AL, Rivkin E, Tres LL. Expression of Fer testis (FerT) tyrosine kinase transcript variants and distribution sites of FerT during the development of the acrosome-acroplaxome-manchette complex in rat spermatids. Dev Dyn 2008; 237(12): 3882-91.
  40. Yu K, Hou L, Zhu JQ, Ying XP, Yang WX. KIFC1 participates in acrosomal biogenesis, with discussion of its importance for the perforatorium in the Chinese mitten crab Eriocheir sinensis. Cell Tissue Res 2009; 337(1): 113-23.
  41. Wang YT, Mao H, Hou CC, Sun X, Wang DH, Zhou H, et al. Characterization and expression pattern of KIFC1-like kinesin gene in the testis of the Macrobrachium nipponense with discussion of its relationship with structure lamellar complex (LCx) and acroframosome (AFS). Mol Biol Rep 2012; 39(7): 7591-8.
  42. Manandhar G, Simerly C, Schatten G. Centrosome reduction during mammalian spermiogenesis. Curr Top Dev Biol 1999; 49: 343-63.
  43. Fishman EL, Jo K, Ha A, Royfman R, Zinn A, Krishnamurthy M, et al. Atypical centrioles are present in Tribolium sperm. Open Biol 2017; 7(3): 160334.
  44. Müjica A, Navarro-García F, Hernández-González EO, de Lourdes Juárez-Mosqueda M. Perinuclear theca during spermatozoa maturation leading to fertilization. Microsc Res Tech 2003; 61(1): 76-87.
  45. Kierszenbaum AL, Rivkin E, Tres LL. Molecular biology of sperm head shaping. Soc Reprod Fertil Suppl 2007; 65: 33-43.
  46. Balhorn R. The protamine family of sperm nuclear proteins. Genome Biol 2007; 8(9): 227.
  47. Dhar S, Thota A, Rao MRS. Insights into role of bromodomain, testis-specific (Brdt) in acetylated histone H4-dependent chromatin remodeling in mammalian spermiogenesis. J Biol Chem 2012; 287(9): 6387-405.
  48. Wu JY, Ribar TJ, Cummings DE, Burton KA, McKnight GS, Means AR. Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4. Nat Genet 2000; 25(4): 448-52.
  49. Sasaki H, Matsui Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet 2008; 9(2): 129-40.
  50. Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res 2008; 314(8): 1892-905.
  51. Pasch E, Link J, Beck C, Scheuerle S, Alsheimer M. The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility. Biol Open 2015; 4(12): 1792-802.
  52. Calvi A, Wong ASW, Wright G, Wong ESM, Loo TH, Stewart CL, et al. SUN4 is essential for nuclear remodeling during mammalian spermiogenesis. Dev Biol 2015; 407(2): 321-30.
  53. Modarres P, Tavalaee M, Ghaedi K, Nasr-Esfahani MH. An overview of the globozoospermia as a multigenic identified syndrome. Int J Fertil Steril 2019; 12(4): 273-7.
  54. Kierszenbaum AL, Rivkin E, Tres LL. Cytoskeletal track selection during cargo transport in spermatids is relevant to male fertility. Spermatogenesis 2011; 1(3): 221-30.
  55. Vogl AW, Weis M, Pfeiffer DC. The perinuclear centriole-containing centrosome is not the major microtubule organizing center in Sertoli cells. Eur J Cell Biol 1995; 66(2): 165-79.
  56. Lehti M, Sironen A. Formation and function of the manchette and flagellum during spermatogenesis. Reproduction 2016; 151(4): R43-54.
  57. Johnson L. Efficiency of spermatogenesis. Microsc Res Tech 1995; 32(5): 385-422.
  58. delBarco-Trillo J, Tourmente M, Roldan ER. Metabolic rate limits the effect of sperm competition on mammalian spermatogenesis. PLoS One 2013; 8(9): e76510.
  59. Niedenberger BA, Chappell VK, Kaye EP, Renegar RH, Geyer CB. Nuclear localization of the actin regulatory protein Palladin in sertoli cells. Mol Reprod Dev 2013; 80(5): 403-13.
  60. Su W, Wong EW, Mruk DD, Cheng CY. The Scribble/Lgl/Dlg polarity protein complex is a regulator of blood-testis barrier dynamics and spermatid polarity during spermatogenesis. Endocrinology 2012; 153(12): 6041-53.
  61. Gao Y, Cheng CY. Does cell polarity matter during spermatogenesis? Spermatogenesis 2016; 6(2): e1218408.
  62. Gao Y, Lui WY, Lee WM, Cheng CY. Polarity protein Crumbs homolog-3 (CRB3) regulates ectoplasmic specialization dynamics through its action on F-actin organization in Sertoli cells. Sci Rep 2016; 6(1): 28589.
  63. Yazama F. Continual maintenance of the blood-testis barrier during spermatogenesis: the intermediate compartment theory revisited. J Reprod Dev 2008:
    54(5): 299-305.
  64. Sha YW, Ding L, Li P. Management of primary ciliary dyskinesia/Kartagener's syndrome in infertile male patients and current progress in defining the underlying genetic mechanism. Asian J Androl 2014; 16(1): 101-6.
  65. Zariwala MA, Leigh MW, Ceppa F, Kennedy MP, Noone PG, Carson JL, et al. Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation. Am J Respir Crit Care Med 2006; 174(8): 858-66.
  66. Sun X, Kovacs T, Hu YJ, Yang WX. The role of actin and myosin during spermatogenesis. Mol Biol Rep 2011; 38(6): 3993-4001.
  67. Kierszenbaum AL, Rivkin E, Tres LL, Yoder BK, Haycraft CJ, Bornens M, et al. GMAP210 and IFT88 are present in the spermatid golgi apparatus and participate in the development of the acrosome-acroplaxome complex, head-tail coupling apparatus and tail. Dev Dyn 2011; 240(3): 723-36.
  68. Hamilton JAM, Cissen M, Brandes M, Smeenk JMJ, De Bruin JP, Kremer J, et al. Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system. Hum Reprod 2015; 30(5): 1110-21.
  69. Cheng Y, Shi X, Yu H, Wu Y, Jia M. Specific expression of beta-actin during spermatogenesis in rats [in Chinese]. Zhonghua Nan Ke Xue 2005; 11(10): 755-60.
  70. Gennerich A, Vale RD. Walking the walk: how kinesin and dynein coordinate their steps. Curr Opin Cell Biol 2009; 21(1): 59-67.
  71. Ma DD, Wang DH, Yang WX. Kinesins in spermatogenesis. Biol Reprod 2017; 96(2): 267-76.
  72. Li YR, Yang WX. Myosin superfamily: The multi-functional and irreplaceable factors in spermatogenesis and testicular tumors. Gene 2016; 576(1 Pt 2): 195-207.
  73. Ji ZY, Sha YW, Ding L, Li P. Genetic factors contributing to human primary ciliary dyskinesia and male infertility. Asian J Androl 2017; 19(5): 515-20.
  74. Kartagener M, Horlacher A. Situs viscerum inversus und Polyposis nasi in einem Falle familiaerer Bronchiektasien. Beitr Klin Tuberk 1936; 87: 331-3.
  75. Afzelius BA. A human syndrome caused by immotile cilia. Science 1976; 193(4250): 317-9.
  76. Barbato A, Frischer T, Kuehni CE, Snijders D, Azevedo I, Baktai G, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J 2009; 34(6): 1264-76.
  77. Kuehni CE, Frischer T, Strippoli MF, Maurer E, Bush A, Nielsen KG, et al. Factors influencing age at diagnosis of primary ciliary dyskinesia in European children. Eur Respir J 2010; 36(6): 1248-58.
  78. Kurkowiak M, Ziętkiewicz E, Witt M. Recent advances in primary ciliary dyskinesia genetics.
    J Med Genet 2015; 52(1): 1-9.
  79. Wambergue C, Zouari R, Mustapha SFB, Martinez G, Devillard F, Hennebicq S, et al. Patients with multiple morphological abnormalities of the sperm flagella due to DNAH1 mutations have a good prognosis following intracytoplasmic sperm injection.
    Hum Reprod 2016; 31(6): 1164-72.
  80. Buchdahl RM, Reiser J, Ingram D, Rutman A, Cole PJ, Warner JO. Ciliary abnormalities in respiratory disease. Arch Dis Child 1988; 63(3): 238-43.
  81. Wilton LJ, Teichtahl H, Temple-Smith PD, De Kretser DM. Structural heterogeneity of the axonemes of respiratory cilia and sperm flagella in normal men. J Clin Invest 1985; 75(3): 825-31.
  82. Lee L. Mechanisms of mammalian ciliary motility: Insights from primary ciliary dyskinesia genetics. Genetics 2011; 473(2): 57-66.
  83. Teves ME, Sears PR, Li W, Zhang Z, Tang W, van Reesema L, et al. Sperm-associated antigen 6 (SPAG6) deficiency and defects in ciliogenesis and cilia function: polarity, density, and beat. PloS One 2014; 9(10): e107271.
  84. Omran H, Häffner K, Völkel A, Kuehr J, Ketelsen UP, Ross UH, et al. Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene. Am J Respir Cell Mol Biol 2000; 23(5): 696-702.
  85. Pennarun G, Chapelin C, Escudier E, Bridoux AM, Dastot F, Cacheux V, et al. The human dynein intermediate chain 2 gene (DNAI2): cloning, mapping, expression pattern, and evaluation as a candidate for primary ciliary dyskinesia. Hum Genet 2000; 107(6): 642-9.
  86. Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, et al. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci U S A 2002; 99(16): 10282-6.
  87. Mazor M, Alkrinawi S, Chalifa-Caspi V, Manor E, Sheffield VC, Aviram M, et al. Primary ciliary dyskinesia caused by homozygous mutation in DNAL1, encoding dynein light chain 1. Am J Hum Genet 2011; 88(5): 599-607.
  88. Castleman VH, Romio L, Chodhari R, Hirst RA, de Castro SCP, Parker KA, et al. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet 2009; 84(2): 197-209.
  89. Chemes HE, Rawe VY. The making of abnormal spermatozoa: cellular and molecular mechanisms underlying pathological spermiogenesis. Cell Tissue Res 2010; 341(3): 349-57.
  90. Brown PR, Miki K, Harper DB, Eddy EM. A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum. Biol Reprod 2003; 68(6): 2241-8.
  91. Turner RM, Johnson LR, Haig-Ladewig L, Gerton GL, Moss SB. An X-linked gene encodes a major human sperm fibrous sheath protein, hAKAP82: genomic organization, protein kinase A-RII binding, and distribution of the precursor in the sperm tail. J Biol Chem 1998; 273(48): 32135-41.
  92. Rawe V, Olmedo SB, Benmusa A, Shiigi SM, Chemes HE, Sutovsky P. Sperm ubiquitination in patients with dysplasia of the fibrous sheath. Hum Reprod 2002; 17(8): 2119-27.
  93. Rives NMD. Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: asthenozoospermia. Cytogenetic Genome Research. Cytogenet Genome Res 2005; 111(3-4): 358-62.
  94. Coutton C, Escoffier J, Martinez G, Arnoult C, Ray PF. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015; 21(4): 455-85.
  95. Viville S, Mollard R, Bach ML, Falquet C, Gerlinger P, Warter S. Do morphological anomalies reflect chromosomal aneuploidies?: Case report. Hum Reprod 2000; 15(12): 2563-6.
  96. O'Donnell L, Rhodes D, Smith SJ, Merriner DJ, Clark BJ, Borg C, et al. An essential role for katanin p80 and microtubule severing in male gamete production. PLoS Genet 2012; 8(5): e1002698.
  97. Barzi NV, Kakavand K, Sodeifi N, Ghezelayagh Z, Sabbaghian M. Expression and localization of Septin 14 gene and protein in infertile men testis. Reprod
    Biol 2020; 20(2): 164-8.
  98. Zhu F, Wang F, Yang X, Zhang J, Wu H, Zhang Z, et al. Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa syndrome. Am J Hum Genet 2016; 99(4): 942-9.
  99. Liška F, Gosele C, Rivkin E, Tres L, Cardoso MC, Domaing P, et al. Rat hd mutation reveals an essential role of centrobin in spermatid head shaping and assembly of the head-tail coupling apparatus. Biol Reprod 2009; 81(6): 1196-205.
  100. Tokuhiro K, Isotani A, Yokota S, Yano Y, Oshio S, Hirose M, et al. OAZ-t/OAZ3 is essential for rigid connection of sperm tails to heads in mouse. PLoS Genet 2009; 5(11): e1000712.
  101. Hosseinifar H, Shafipour M, Modarresi T, Azad M, Sadighi Gilani MA, Shahhosseini M, et al. Relationship between absence of annulus and asthenozoospermia in Iranian men. J Assist Reprod Genet 2014; 31(12): 1681-5.
Journal of Isfahan Medical School
Volume 40, Issue 690
2nd Week, December
November and December 2022
Pages 800-817

Files

Share

How to cite

Statistics