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Bulls are helping solve the mysteries of male infertility

In the quest to unravel the complexities of male infertility, a research team led by Professor Hubert Pausch of ETH Zurich has turned to an unlikely source for insights: bulls

The research not only sheds light on the genetic underpinnings of male fertility but also paves the way for potential advancements in human fertility research and livestock breeding practices.

Study background 

Infertility affects approximately one in eight couples globally, with male fertility issues contributing to half of these cases. However, identifying the genetic causes behind such fertility disorders in humans has been a significant challenge due to the lack of comprehensive data on semen quality and molecular markers from large cohorts of healthy, reproductive-aged men. 

This gap in knowledge has led researchers to explore alternative avenues, with the study on young bulls emerging as a pivotal step towards understanding the genes and mechanisms controlling male fertility.

Focus of the research 

The researchers analyzed tissue samples from the testicles, epididymis, and vas deferens of 118 freshly slaughtered bulls of reproductive age. Importantly, these animals were not killed specifically for the study, mitigating ethical concerns. 

Based on their analysis, the experts were able to characterize the transcriptomes – the complete set of messenger RNA molecules – of the tissues. This made it possible to identify active genes within the reproductive organs and their impact on fertility.

Key insights

The study revealed a multitude of genes and their variants associated with fertility in bulls, many of which are also likely relevant to human male fertility. According to Xena Mapel, the study’s first author, the regulation of male fertility is “highly conserved” across mammals, suggesting a fundamental similarity in reproductive gene function among species. 

“These genes are closely linked to poor fertility in bulls,” said Mapel. “Such subfertile bulls don’t show up during conventional ejaculate screening. However, they can be reliably detected with our new marker genes.”

Challenges of studying male fertility

Cattle, despite being an unconventional choice for such studies, offer unique advantages. Their genetic makeup is well-documented, and the regular collection and analysis of ejaculate for breeding purposes provide a rich data source for research. 

This contrasts with the challenges of studying human male fertility, where data comparability and the invasive nature of obtaining reproductive tissue samples pose significant obstacles.

“We don’t know what influences the men were exposed to before they took the fertility test, which will be different for every test subject. Furthermore, it’s practically impossible to obtain tissue samples from their reproductive tract, as that would entail an invasive medical procedure,” noted the researchers.

The greatest advantage of the bull cohort analyzed for the study is that all the animals are similar in age. “This cohort is very homogeneous. If we had to carry out a comparable study on men, we’d have to rely on voluntary donors, potentially across all possible age groups. This would give us data that’s very difficult to compare.”

Study implications 

For human fertility studies, while the immediate application of these findings remains uncertain, they offer a promising foundation for future research into the genetic factors influencing male fertility. 

On the other hand, livestock breeders stand to benefit directly from these insights. By integrating the new genetic markers into bull breeding programs, breeders can more accurately identify fertile bulls, significantly reducing the financial losses associated with unsuccessful artificial inseminations.

Artificial insemination is a cornerstone of modern livestock breeding, with around 800,000 cows artificially inseminated annually in Switzerland alone. 

The economic impact of using semen from subfertile bulls is substantial, not only in terms of the direct costs of insemination but also due to the broader financial implications of reduced milk production and the need to replace non-pregnant cows. The study’s findings have the potential to enhance breeding efficiency and sustainability in the livestock industry.

The study is published in the journal Nature Communications

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