The Molecular Landscape of Spermatogonial Stem Cell Renewal, Meiotic Sex Chromosome Inactivation, and Spermatic Head Shaping

  • Laura L. Tres
  • Abraham L. Kierszenbaum

Spermatogenesis is a hormonally regulated process involving three sequential events: (1) the mitotic amplification of the spermatogonial cell progeny, (2) the completion of meiosis by the spermatocyte progeny, and (3) spermiogenesis, the gradual morphogenesis of the spermatid progeny. Mitosis, meiosis and spermiogenesis coexist in the seminiferous epithelium in association with a post-mitotic stable population of somatic Sertoli cells. Cell components of each spermatogonial, spermatocyte, and spermatid cell progeny remain connected by intercellular cytoplasmic bridges. Intercellular bridges are disrupted upon completion of spermiogenesis leading to the release in the seminiferous tubular lumen of single mature spermatids transported to the epididymal duct for acquisition of fertilizing activity. Several key cell cycle regulators have been shown to operate during the mitotic amplification of the spermatogonial progeny. During meiotic prophase, autosomal bivalents are engaged in prominent ribosomal RNA and non-ribosomal RNA transcriptional activity, in contrast with the transcriptional silencing of the condensed XY chromosomes. An autosomal bivalent is a synapsed (conjoined) chromosomal pair, excluding the sex chromosomes X and Y, observed during meiotic prophase I. Each member of a chromosomal bivalent (autosomes and X-Y) consists of two sister chromatids that will disjoin (separate) upon completion of meiosis to produce a haploid genome (spermatid). During spermiogenesis, gradual genetic inactivation of the spermatid genome correlates with spermatid head shaping. The acrosome-acroplaxome-manchette complex is emerging as a significant player in spermatid head shaping as well as in the assembly of the sperm head–tail coupling apparatus and the development of the outer dense fiber-axoneme-containing sperm tail. The acroplaxome is a cytoskeletal plate bordered by a desmosome-like marginal ring fastening the descending recess of the acrosomal sac to the nuclear envelope of the spermatid. The manchette is a transient microtubular-containing structure developed beneath the acroplaxome and encircling the elongating spermatid nucleus. This chapter is restricted to recent developments in the bioregulation of the spermatogonial stem cell progeny, the process of transcriptional inactivation of the XY bivalent, and the steps leading to spermatid head shaping. These are three relevant aspects that, when disrupted, can lead to male infertility.


Sertoli Cell Synaptonemal Complex Meiotic Prophase Seminiferous Epithelium Spermatogonial Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


27.7Glossary of Terms and Acronyms


DNA repair protein, member of the PI3-kinase-like family


breast cancer 1 gene


cellular homolog of the feline sarcoma viral oncogene v-kit

cyclin D1 and D2:

cell cycle-regulatory genes


double-strand breaks


follicle stimulating hormone


glial cell line-derived neurotrophic factor


Golgi-associated PDZ and coiled-coil motif containing


H2A histone family, member Y (also known as histone macroH2A1)


variant of the histone H2a


Asn-Pro-Phe (NPF) motif-containing protein (also called Rab or hRip)


human immunodeficiency virus Rev-interacting protein.


kinesin family member C


meiotic autosomal nucleolar organization


meiotic sex chromosome inactivation


meiotic recombination 11 protein


Nijmegen breakage syndrome 1


Outer dense fiber 2


promyelocytic leukemia zinc-finger, a transcriptional repressor encoded by the Zfp145 gene


Poxviruses and zinc-finger (POZ) and Krüppel family of transcription repressors


Poxviruses and zinc-finger


member of the Ras superfamily of monomeric G proteins


a DNA helicase repair protein


Mre11-interacting protein with binding affinity to double stranded DNA.


protooncogene tyrosine kinase receptor that binds members of the GDNF family

Ssty 1 and Ssty 2:

Y-linked spermiogenesis specific transcript


zinc finger protein 145 gene


  1. 1.
    Kierszenbaum AL. Spermatogenesis. In: Kierszenbaum AL. Histology and Cell Biology: An Introduction to Pathology, Second edition. Philadelphia:Mosby, 2007:569–96.Google Scholar
  2. 2.
    Meng X, Lindahl M, Hyvönen ME, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science2000; 287:1489–93.PubMedCrossRefGoogle Scholar
  3. 3.
    Jijiwa M, Kawai K, Fukihara J, et al. GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells. Genes Cells 2008; 13:365–74.PubMedCrossRefGoogle Scholar
  4. 4.
    Costoya JA. Functional analysis of the role of POK transcriptional repressor. Brief Funct Genomic Proteomic 2007; 6:8–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Tres LL, Kierszenbaum AL. The ADAM-integrin-tetraspanin complex in fetal and postnatal testicular cords. Birth Defects Res C Embryo Today 2005; 75:130–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Beumer TL, Roepers-Gajadien HL, Gademan IS, et al. Involvement of the D-type cyclins in germ cell proliferation and differentiation in the mouse. Biol Reprod 2000; 63:1893–98.PubMedCrossRefGoogle Scholar
  7. 7.
    Costoya JA, Hobbs RM, Barna M, et al. Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet 2004; 36:653–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Buaas FW, Kirsh AL, Sharma M, et al. Plzf is required in adult male germ cells for stem cell self-renewal. Nat Genet 2004; 36:647–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Filipponi D, Hobbs RM, Ottolenghi S, et al. Repression of kit expression by Plzf in germ cells. Mol Cell Biol 2007; 27: 6770–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Kierszenbaum AL. Mammalian spermatogenesis in vivo and in vitro: a partnership of spermatogenic and somatic cell lineages. Endocr Rev 1994; 15:116–34.PubMedGoogle Scholar
  11. 11.
    Marh J, Tres LL, Yamazaki Y, et al. Mouse round spermatids developed in vitro from preexisting spermatocytes can produce normal offspring by nuclear injection into in vivo-developed mature oocytes. Biol Reprod 2003; 69:169–76.PubMedCrossRefGoogle Scholar
  12. 12.
    Borde V. The multiple roles of the Mre11 complex for meiotic recombination. Chromosome Res 2007; 15:551–63.PubMedCrossRefGoogle Scholar
  13. 13.
    Page SL, Hawley RS. The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 2004; 20:525–58.PubMedCrossRefGoogle Scholar
  14. 14.
    Tres LL. XY chromosomal bivalent: nucleolar attraction. Mol Reprod Dev 2005; 72:1–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Namekawa SH, Park PJ, Zhang LF, et al. Postmeiotic sex chromatin in the male germline of mice. Curr Biol 2006; 16:660–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Fernandez-Capetillo O, Mahadevaiah SK, Celeste A, et al. H2AX is required for chromatin remodeling and inactivation of sex chromosomes in male mouse meiosis. Dev Cell 2003; 4: 497–508.Google Scholar
  17. 17.
    Mahadevaiah SK, Turner JM, Baudat F, et al. Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 2001; 27:271–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Turner JM, Mahadevaiah SK, Fernandez-Capetillo O, et al. Silencing of unsynapsed meiotic chromosomes in the mouse. Nat Genet 2005; 37:41–7.PubMedGoogle Scholar
  19. 19.
    Turner JM, Aprelikova O, Xu X, et al. BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Curr Biol 2004; 14:2135–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Turner JMA. Meiotic sex chromosome inactivation. Development 2007; 134:1823–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Rivkin E, Tres LL, Kierszenbaum AL. Genomic origin, processing and developmental expression of testicular outer dense fiber 2 (ODF2) transcripts and a novel nucleolar localization of ODF2 protein. Mol Reprod Dev 2008; 75:1591–602.Google Scholar
  22. 22.
    Salmon NA, Reijo Pera RA, Xu EY. A gene trap knockout of the abundant sperm tail protein, outer dense fiber 2, results in preimplantation lethality. Genesis 2006; 44:515–22.CrossRefGoogle Scholar
  23. 23.
    Kierszenbaum AL, Tres LL. The acrosome-acroplaxome-manchette complex and the shaping of the spermatid head. Arch Histol Cytol 2004; 67:271–84.PubMedCrossRefGoogle Scholar
  24. 24.
    Kierszenbaum AL, Rivkin E, Tres LL. Molecular biology of sperm head shaping. Soc Reprod Fertil Suppl 2007; 65:33–43.PubMedGoogle Scholar
  25. 25.
    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: 4628–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Kierszenbaum AL. Intramanchette transport (IMT): managing the making of the spermatid head, centrosome, and tail. Mol Reprod Dev 2002; 63:1–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Touré A, Szot M, Mahadevaiah SK, et al. A new deletion of the mouse Y chromosome long arm associated with the loss of Ssty expression, abnormal sperm development and sterility. Genetics 2004; 166:901–12.PubMedCrossRefGoogle Scholar
  28. 28.
    Kang-Decker N, Mantchev GT, Juneja SC, et al. Lack of acrosome formation in Hrb-deficient mice. Science 2001; 294:1531–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Yao R, Ito C, Natsume Y, et al. Lack of acrosome formation in mice lacking a Golgi protein, GOPC. Proc Natl Acad Sci U S A 2002; 99:11211–6.CrossRefGoogle Scholar
  30. 30.
    Yang WX, Sperry AO. C-terminal kinesin motor KIFC1 participates in acrosome biogenesis and vesicle transport. Biol Reprod 2003; 69:1719–29.PubMedCrossRefGoogle Scholar
  31. 31.
    Langford GM. Myosin-V, a versatile motor for short-range vesicle transport. Traffic 2002; 3:859–65.PubMedCrossRefGoogle Scholar
  32. 32.
    Seabra MC, Mules EH, Hume AN. Rab GTPases, intracellular traffic and disease. Trends Mol Med 2002; 8:23–30.PubMedCrossRefGoogle Scholar
  33. 33.
    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; 103:337–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Cell Biology and AnatomyThe Sophie Davis School of Biomedical Education, The City University of New York Medical SchoolNew YorkUSA

Personalised recommendations