Interdisciplinary research challenges long-held belief about sperm function

For decades, scientists believed that once sperm were ejaculated they could no longer synthesize new proteins — in other words, they became “silent.”

A new study from the University of Calgary, published in Communications Biology (Nature Portfolio), challenges that long-held belief. 

The research provides evidence that sperm retain the molecular machinery needed to regulate protein synthesis — even after leaving the testes. 

The research was led by PhD candidate Saurabh Tiwari under the co-supervision of Dr. Jacob Thundathil, PhD, DVM, a professor in UCalgary’s Faculty of Veterinary Medicine, and Dr. Nehal Thakor, PhD, a professor at the University of Lethbridge. 

Using bull sperm as a model, the team investigated physiology of sperm “capacitation” - the final stage of sperm maturation, at which point sperm gain the ability to fertilize. During this process, which occurs after sperm are deposited in the female reproductive tract, they undergo biochemical changes that enable them to penetrate and fertilize the egg. 

Through advanced molecular analyses, the research team identified in sperm the presence of molecular machinery that could regulate when and which proteins are synthesized, and fine-tune their performance on their journey to fertilization. 

Why it matters

Male factors account for roughly half of all fertility challenges in humans. Yet, many cases remain unexplained. 

This study advances the fundamental understanding of sperm function, opening the door to developing diagnostic tools that assess male fertility at the molecular level and address the unexplained fertility issues. 

The findings also have major implications for the livestock industry. 

In animal breeding, semen from elite bulls is used to inseminate thousands of cows. Current evaluation techniques often fail to distinguish between fertile and subfertile bulls — a problem that can reduce conception rates and lead to significant economic loss. 

This research could help identify new molecular markers of fertility, improving both human and animal reproductive outcomes.

Next steps 

The research team is now working to identify the specific proteins synthesized in sperm and how these are linked to successful fertilization and embryo development. 

They also aim to understand why only certain proteins are produced in sperm during capacitation and how these mechanisms vary among males with different fertility levels. 

The combined expertise and resources of Thundathil and Thakor will be used to conduct these mechanistic studies; the Thakor Lab at the U of L is renowned for its expertise in RNA research. 

The research was funded by a grant awarded to Thundathil from the Natural Sciences and Engineering Research Council of Canada. Read the full study.