X Chromosome and Spermatogenesis Defects


Spermatogenesis, the process through which mature spermatozoa are formed, is a complex process requiring a very strict regulation. More than 2000 genes are involved in spermatogenesis. Part of these genes has a unique function during spermatogenesis. The X chromosome is special because only one copy is present in men, whereas women have two X copies. Moreover, the mammalian X chromosome is enriched for testis‐specific genes. This makes the X chromosome particularly interesting in view of male infertility. Although multiple studies have tried to identify mutations in X‐linked spermatogenesis genes, the number of causative mutations detected so far remains low. Nowadays, new techniques allow the analysis of the complete X chromosome in a single experiment. Within the next few years, the knowledge on the role of the X chromosome in male infertility (and consequently also in spermatogenesis) will increase.

Key Concepts:

  • Men are hemizygous for X‐chromosomal genes: men only have one X chromosome; mutations in X‐linked genes (might) have an immediate impact on spermatogenesis.

  • Spermatogenic failure can be caused by genetic defects.

  • The X chromosome is enriched for spermatogenesis genes.

  • Many multi‐copy genes involved in spermatogenesis are also expressed in cancer cell lines. Therefore, these are often described as cancer‐testis (CT) genes.

  • Many X‐linked genes that are preferentially expressed in testis have not (yet) been evaluated in view of male infertility.

  • The study of individual genes in view of male infertility has been disappointing because it is a time‐consuming process and often no differences with normal controls have been detected.

Keywords: X chromosome; spermatogenesis; mutations; infertility; genetics; polymorphisms; genes

Figure 1.

Comparison of the X and Y chromosomes.

Figure 2.

Array CGH: example of a CNV present on the X chromosome.



Akinloye O, Gromoll J, Callies C, Nieschlag E and Simoni M (2007) Mutation analysis of the X‐chromosome linked, testis‐specific TAF7L gene in spermatogenic failure. Andrologia 39(5): 190–195.

Aston KI and Carrell DT (2009) Genome‐wide study of single‐nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. Journal of Andrology 30(6): 711–725.

Cheng Y, Buffone MG, Kouadio M et al. (2007) Abnormal sperm in mice lacking the Taf7l gene. Molecular and Cellular Biology 27(7): 2582–2589.

Dirac AM and Bernards R (2010) The deubiquitinating enzyme USP26 is a regulator of androgen receptor signaling. Molecular Cancer Research 8(6): 844–854.

Krausz C, Giachini C, Lo Giacco D et al. (2012) High resolution X chromosome‐specific array‐CGH detects new CNVs in infertile males. PLoS One 7(10): e44887.

Lee J, Park HS, Kim HH et al. (2009) Functional polymorphism in H2BFWT‐5′UTR is associated with susceptibility to male infertility. Journal of Cellular and Molecular Medicine 13(8B): 1942–1951.

Lin YW, Hsu TH and Yen PH (2011) Localization of ubiquitin specific protease 26 at blood‐testis barrier and near Sertoli cell‐germ cell interface in mouse testes. International Journal of Andrology 34(5 Pt 2): e368–e377.

Massart A, Lissens W, Tournaye H and Stouffs K (2012) Genetic causes of spermatogenic failure. Asian Journal of Andrology 14(1): 40–48.

Olesen C, Silber J, Eiberg H et al. (2003) Mutational analysis of the human FATE gene in 144 infertile men. Human Genetics 113(3): 195–201.

Pan J, Eckardt S, Leu NA et al. (2009) Inactivation of Nxf2 causes defects in male meiosis and age‐dependent depletion of spermatogonia. Developmental Biology 330(1): 167–174.

Ravel C, El Houate B, Chantot S et al. (2006) Haplotypes, mutations and male fertility: the story of the testis‐specific ubiquitin protease USP26. Molecular Human Reproduction 12(10): 643–646.

Skaletsky H, Kuroda‐Kawaguchi T, Minx PJ et al. (2003) The male‐specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423(6942): 825–837.

Stouffs K and Lissens W (2012) X chromosomal mutations and spermatogenic failure. Biochimica et Biophysica Acta 1822(12): 1864–1872.

Stouffs K, Lissens W, Tournaye H, Van Steirteghem A and Liebaers I (2005) Possible role of USP26 in patients with severely impaired spermatogenesis. European Journal of Human Genetics 13(3): 336–340.

Stouffs K, Tournaye H, Liebaers I and Lissens W (2009) Male infertility and the involvement of the X chromosome. Human Reproduction Update 15(6): 623–637.

Stouffs K, Tournaye H, Van der Elst J, Liebaers I and Lissens W (2008) Is there a role for the nuclear export factor 2 gene in male infertility? Fertility and Sterility 90(5): 1787–1991.

Stouffs K, Vandermaelen D, Massart A et al. (2012) Array comparative genomic hybridization in male infertility. Human Reproduction 27(3): 921–929.

Stouffs K, Willems A, Lissens W et al. (2006) The role of the testis‐specific gene hTAF7L in the aetiology of male infertility. Molecular Human Reproduction 12(4): 263–267.

Turner RM, Musse MP, Mandal A et al. (2001) Molecular genetic analysis of two human sperm fibrous sheath proteins AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath, Journal of Andrology 22(2): 302–315.

Tüttelmann F, Simoni M, Kliesch S et al. 2009. Copy number variants in patients with severe oligozoospermia and Sertoli‐cell‐only syndrome. PLoS One 6(4): e19426.

Vallender EJ and Lahn BT (2004) How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26(2): 159–169.

Visser L, Westerveld GH, Xie F et al. (2011) A comprehensive gene mutation screen in men with asthenozoospermia. Fertility and Sterility 95(3): 1020–1024.

Wang PJ, McCarrey JR, Yang F and Page DC (2001) An abundance of X‐linked genes expressed in spermatogonia. Nature Genetics 27(4): 422–426.

Zhang YE, Vibranovski MD, Landback P, Marais GA and Long M (2010) Chromosomal redistribution of male‐biased genes in mammalian evolution with two bursts of gene gain on the X chromosome. PLoS Biology 8(10): e1000494.

Zhou J, McCarrey JR and Wang PJ (2013) A 1.1‐mb segmental deletion on the X chromosome causes meiotic failure in male mice. Biology of Reproduction 88(6): 159.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Stouffs, Katrien, and Lissens, Willy(Nov 2013) X Chromosome and Spermatogenesis Defects. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025311]