Journal of Andrology
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Published-Ahead-of-Print October 29, 2009, DOI:10.2164/jandrol.109.008193

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Regulation of Male Fertility by X-Linked Genes

Ke Zheng , Fang Yang , and P. Jeremy Wang *

* To whom correspondence should be addressed. E-mail: pwang{at}vet.upenn.edu.

Infertility is a worldwide reproductive health problem, affecting men and women roughly equally. Mouse genetic studies demonstrate that more than two hundred 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 Akap4, Nxf2, Taf7l, and Tex11, indeed play important roles in regulation of male fertility. Moreover, we find that the Taf7l Tex11 double mutant males exhibited much more severe defects in meiosis than either single mutant, suggesting that these two 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.


Key words: Fertility • Infertility • Reproductive Genetics • Spermatogenesis • Testis • X chromosome • meiosis




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