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27-05-2012 | Genetics | Article

Gene critical to male fertility discovered


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MedWire News: Researchers have discovered a gene - KATNAL1 - that is vitally important for the development of healthy sperm.

"If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive," said study author Lee Smith (University of Edinburgh, UK) in a press statement.

"The important thing is that the effects of such a drug would be reversible because KATNAL1 only affects sperm cells in the later stages of development, so it would not hinder the early stages of sperm production and the overall ability to produce sperm."

Smith and team used a chemical treatment to induce random genetic mutations in male mice prior to birth, and then selected mice that were infertile for further analysis.

Gene-mapping techniques were used to find out which chromosome the relevant mutation was located on, and DNA sequencing was then used to map the mutation, which was in the mouse version of the KATNAL1 gene (Katnal1). The mutation resulted in Katnal1 becoming nonfunctional due to a leucine to valine amino acid substitution.

Further research in mice and human tissue revealed that KATNAL1 is expressed in sperm cell supporting Sertoli cells. The KATNAL1 protein acts to control Sertoli cell microtubule formation, breakdown, and rebuilding, and controls retention of sperm cells during their maturation.

When the gene is nonfunctional, immature sperm are released prematurely, resulting in male infertility. The only phenotypic sign of this mutation was reduced testis weight in the mice, due to a lower number of postmeiotic germ cells resulting from premature release of infertile, immature sperm.

"The identification and characterization of this gene, the first microtubule severing protein shown to function in Sertoli cells, will further our understanding of how male fertility is promoted, while also providing important information relevant to the development of male contraceptives," write the authors in PLoS Genetics.

"Although other research is being carried out into non-hormonal male contraceptives, identification of a gene that controls sperm production in the way KATNAL1 does is a unique and significant step forward in our understanding of testis biology," Smith told the press.

By Helen Albert

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