Learning how infection and inflammation can affect male fertility

Important new details have been discovered about sperm production and the potential for fertility to be diminished in men with infections in the male reproductive tract, due to changes in the immune cells that support healthy testis functions.

Sivanjah Indumathy

It is hoped the new information will lead to improved monitoring and treatment of male fertility issues.

The  Hudson Institute of Medical Research-led study published in the Journal of Reproductive Immunology, analysed immune cells in a healthy adult testis and gained insights into how these cells’ function may change in response to disease-causing bacteria.

The study led by PhD student, Sivanjah Indumathy , and her co-supervisors Professor Kate Loveland and Professor Mark Hedger, Research Group Heads in the Centre for Reproductive Health, examined the nature of macrophages – specialised cells essential for normal organ function that are involved in the detection and destruction of harmful organisms such as bacteria, but that can also promote inflammation.

Prof Loveland likened macrophages and immune cells to a police force: normally the system works to ensure we live and travel safely but is activated and changes function in an emergency.

These results shed light on how macrophages support normal testis function and how they may be primed to respond to external threats.

“Our study highlights the potential for fertility to be reduced in men both while they have infections, and also after the infection has cleared. These infections in the male reproductive tract can influence their immune cell status and activity,” said Ms Indumathy.

Prof Loveland said male infertility affects one in 20 men and is increasingly common.

“We understand very little about why male fertility is declining, so we are building fundamental knowledge about how sperm form in the healthy testis and how immune cells contribute to male reproductive fitness,” Prof Loveland said.

Male fertility under the microscope

Professor Kate Loveland from the Testis Development and Male Germ Cell Biology Research Group at Hudson Institute
Professor Kate Loveland

Immune cells are important for maintaining a healthy environment for sperm production, but these cells’ activity must also be held in check to ensure maturing sperm are not recognised as foreign.

The researchers discovered new information about the role of activin A, a protein and key regulator of reproductive health that acts widely in the body to support normal organ functioning. Activin A levels can change during infections (bacterial, microbial and viral).

The study confirmed that most of the immune cells in testes are macrophages, but multiple rare subsets were discovered for the first time in the testis. Importantly, testes with higher- than-normal activin A levels had a higher proportion of macrophages likely to be involved in inflammation – placing sperm production in peril.

“This provides an important indication of how the increased activin A levels which can occur during infection and inflammation may activate the testicular immune system,” said Prof Loveland.  “Some of these immune cell subsets and the effect of activin A on their activities have not been identified before,” she said.

Next steps

The team will now look in more detail at how higher and lower levels of activin A change macrophage function and the production of sperm.

The researchers hope to understand if this information can be harnessed to control immune reactions when there is damage to the testis or systemic disease that could impair fertility.

Adult testis tubule in cross sectionTwo different types of macrophages (shown here as green cells) were photographed and counted in the adult preclinical model testis, using a confocal microscope to reveal their shapes. The right-hand panel shows macrophages with thin processes, shaped like stars, surrounding the tubules inside which sperm develop. The left-hand panel shows the more rounded or polygonal macrophages in the spaces between the tubules.

Collaborators
Monash University Justus-Liebig University, Germany; Ohana Biosciences, USA; Burnet Institute

Funder
NHMRC

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