Regulation of male fertility by X-linked genes

J Androl. Jan-Feb 2010;31(1):79-85. doi: 10.2164/jandrol.109.008193. Epub 2009 Oct 29.


Infertility is a worldwide reproductive health problem, affecting men and women about equally. Mouse genetic studies demonstrate that more than 200 genes specifically or predominantly regulate fertility. However, few genetic causes of infertility in humans have been identified. Here, we focus on the regulation of male fertility by X-linked, germ cell-specific genes. Previous genomic studies reveal that the mammalian X chromosome is enriched for genes expressed in early spermatogenesis. Recent genetic studies in mice show that X-linked, germ cell-specific genes, such as A-kinase anchor protein 4 (Akap4), nuclear RNA export factor 2 (Nxf2), TBP-associated factor 7l (Taf7l), and testis-expressed gene 11 (Tex11), indeed play important roles in the regulation of male fertility. Moreover, we find that the Taf7l Tex11 double-mutant males exhibit much more severe defects in meiosis than either single mutant, suggesting that these 2 X-linked genes regulate male meiosis synergistically. The X-linked, germ cell-specific genes are particularly attractive in the study of male infertility in humans. Because males are hemizygous for X-linked genes, loss-of-function mutations in the single-copy X-linked genes, unlike in autosomal genes, would not be masked by a normal allele. The genetic studies of X-linked, germ cell-specific genes in mice have laid a foundation for mutational analysis of their human orthologues in infertile men.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • A Kinase Anchor Proteins / metabolism
  • Animals
  • Cell Cycle Proteins
  • Fertility / genetics*
  • Genes, X-Linked*
  • Humans
  • Infertility, Male / genetics*
  • Male
  • Meiosis
  • Mice
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Proteins / metabolism
  • RNA-Binding Proteins / metabolism
  • Sperm Motility
  • Spermatozoa / physiology
  • Stem Cells / physiology


  • A Kinase Anchor Proteins
  • Akap4 protein, mouse
  • Cell Cycle Proteins
  • Nucleocytoplasmic Transport Proteins
  • Nxf2 protein, mouse
  • Proteins
  • RNA-Binding Proteins
  • Tex11 protein, mouse