Finding answers to the causes of male infertility

By Rob Clancy, staff writer

Major step for male infertility diagnoses and treatment

A world-first sighting of ‘sneaky’ sperm particles outside their usual ‘home’ in the testes offers hope for the one in 10 infertile men and new insight for cancer researchers.

Dr Liza O’Donnell

Dr Liza O’Donnell’s surprising discovery was that sperm-derived proteins can enter the bloodstream, providing the rationale for a simple blood test for infertile men, instead of an invasive biopsy.

“This new knowledge represents a major step forward to advance infertility diagnosis and treatment,” says Dr O’Donnell.

The finding debunks the established belief that sperm-specific proteins are confined to testes’ sperm-producing tubules. Instead, the team found that they are released into surrounding testicular fluid and can circulate in the blood.

“My first thought was ‘uh oh, someone has made a mistake’!” says Dr O’Donnell. “But the findings were confirmed in different ways, and we can share this exciting discovery with the world.”

Huge advances in proteomics technologies that measure thousands of proteins in biological fluids made the discovery possible. The findings may enable a blood test to measure sperm-producing capacity and guide sperm retrieval for IVF procedures.

“Other benefits include helping men who can’t provide a sperm sample due to religious beliefs, and aiding research into male contraceptives and the environmental impacts on fertility.

“It could also inform cancer research and treatment. Many of the sperm-specific proteins found in the testes fluid are also known as cancer testis antigens, which are biomarkers and targets for cancer therapy,” she says.

Collaborators | University of Newcastle; WEHI; Justus-Liebig University, Germany

Funders | National Health and Medical Research Council (NHMRC)

Published in The FASEB Journal.

Significant cause of unexplained male infertility

Better understanding the immune system, from wards off invaders to the ways it can sabotage itself, has brought enormous benefits to humanity – and has now shed light on a significant cause of unexplained male infertility.

L-R: Professor Mark Hedger, Dr Rukmali Wijayarathna

It was a previous immune system discovery that led Dr Rukmali Wijayarathna to identify a significant cause of male infertility and, potentially, a new basis for male contraception. Her findings were published in the journal, Andrology.

Sperm grow in the testes, but it is in the organ known as the epididymis where they acquire the ability to fertilise an egg. The epididymis has a unique immune environment that prevents the body identifying sperm as ‘foreign’ and attacking them.

However, Dr Wijayarathna, a postdoctoral researcher working with Professor Mark Hedger, found that if there is a blockage in the tubes between the testis and the epididymis, that environment changes, making it hostile for sperm survival and maturation.

“Currently, 40 per cent of infertile men worldwide are diagnosed with unexplained or ‘idiopathic’ infertility, where the cause is unknown,” she says.

“What we have identified is potentially not just a significant cause of previously unexplained male infertility, it could also be a starting point in the development of new forms of male contraception.”

While male infertility is on the rise, the need for effective male contraceptives remains unmet. These findings could have a significant impact on both those challenges.

Collaborators | Justus-Liebig University, Germany; Oxford-Brookes University, UK; University of Virginia, USA

Funders | National Health and Medical Research Council (NHMRC)

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