A new type of male contraceptive could be created thanks to the discovery of a key gene essential for sperm development.
The finding could lead to alternatives to the conventional male contraceptives that rely on disrupting the production of hormones, such as testosterone. These treatments can cause side-effects such as irritability, mood swings and acne.
Research, led by the University of Edinburgh, has shown how a gene – Katnal1 – is critical to enable sperm to mature in the testes.
If scientists can regulate the Katnal1 gene in the testes, they could prevent sperm from maturing completely, making them ineffective without changing hormone levels.
The research, which is published in the journal PLoS Genetics, could also help in finding treatments for cases of male infertility when malfunction of the Katnal1 gene hampers sperm development.
Dr Lee Smith, Reader in Genetic Endocrinology at the University of Edinburgh's Centre for Reproductive Health, said: "If we can find a way to target this gene in the testes, we could potentially develop a non-hormonal contraceptive.
"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.
"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."
Scientists found that male mice that were modified so they did not have the Katnal1 gene were infertile.
Further investigation showed that this was because the gene was needed to allow the sperm to develop and mature.
The researchers showed that Katnal1 was needed to regulate the scaffolding structures known as microtubules, which form part of the cells that support and provide nutrients to developing sperm.
Breaking down and rebuilding these microtubules enables the sperm cells to move within the testes as they mature. Katnal1 acts as the essential controller of this process.
FINANCIAL DISCLOSURE: This work was funded by independent UK Medical Research Council Programme Grants to LBS and JP (www.mrc.ac.uk). MKO and LO were funded by a project grant from the National Health and Medical Research Council (www.nhmrc.gov.au) of Australia. MKO is the recipient of an NHMRC Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
CITATION: Smith LB, Milne L, Nelson N, Eddie S, Brown P, et al. (2012) KATNAL1 Regulation of Sertoli Cell Microtubule Dynamics Is Essential for Spermiogenesis and Male Fertility. PLoS Genet 8(5): e1002697. doi:10.1371/journal.pgen.1002697
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