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Protein defect trims sperms’ tails

MONASH U. (AUS) — A dysfunctional protein can result in sperm with shorter tails and limited swimming ability, researchers say.

The new insights into sperm swimming skills shed light on male infertility, which affects one in 20 men, and could provide a new avenue to the development of a male contraceptive pill.

In a study published in the journal PLoS Genetics, researchers from Monash University and their colleagues in the UK and Australia have shown how a protein called RABL2 affects the length of sperm tails, crippling their motility—or swimming ability—and decreases sperm production.

Professor Moira O’Bryan from Monash University’s School of Biomedical Sciences led the research. In laboratory tests, the team found that a mutation in RABL2 resulted in sperm tails that were 17 percent shorter than normal.

Dysfunctioning RABL2 also negatively affected sperm production, resulting in a 50 percent decrease.

O’Bryan says the research fits another piece in the jigsaw puzzle of sperm development.

“The mutations in the RABL2 gene are very likely to cause infertility,” O’Bryan says.

“Further, as motility is absolutely essential for fertility, insights into tail function may reveal options for urgently needed male-based contraception.”

Lead author and PhD student Jennifer Lo, also from the School of Biomedical Sciences, says RABL2 worked with other molecules known as intraflagellar transport proteins that carry genetic cargo along the sperm tail.

“Intraflagellar transport proteins are like a train. Our data suggests that the reloading of the train is defective if RABL2 dysfunctions,” Lo says.

“The train is still running in sperm tails with dysfunctional RABL2, but it contains fewer passengers. The end result is that sperm formation and motility are abnormal.”

Lo says that as mutations in RABL2 decrease sperm count and sperm swimming ability, it may be possible to inhibit this protein in a future male pill.

However, as RABL2 is also found—though in lower concentrations—in other tissues, such as the brain, kidney, and liver, an inhibitor specific to the testes would be necessary.

O’Bryan says that male infertility was often the canary in the coal mine of general health.

“Many of the basic processes of sperm development occur at lower levels in other organs of the body. As such, the presentation of a man for infertility treatment offers the opportunity not only to give him the children he desires but also to mitigate future disease,” O’Bryan says.

Co-authors of the study contributed from Australia’s University of Newcastle, John Curtin School of Medical Research, and Garvan Institute of Medical Research, as well as the University of Cambridge.

The NHMRC, the Australian Research Council, the New South Wales Cancer Council, Cancer Institute New South Wales, Banque Nationale de Paris-Paribas Australia and New Zealand, RT Hall Trust, and the National Breast Cancer Foundation supported the study.

Source: Monash University

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