Zinc Key Regulator of Sperm Functions During Capacitation Process

Findings have implications for improving fertility outcomes in animals and humans.

Findings have implications for improving fertility outcomes in animals and humans.

Scientists have struggled to fully understand how male sperm cells function and why they sometimes fail to fertilize female eggs, which has implications for both livestock farmers aiming to maximize food production, as well as human couples struggling with infertility.

In a new study at the University of Missouri, researchers found that zinc ion plays a crucial regulatory role in the sperm capacitation process, or series of changes sperm undergo in the female reproductive tract that enable them to fertilize an egg.

Michal Zigo, a research scientist at the MU College of Agriculture, Food and Natural Resources (CAFNR), from the laboratory of Peter Sutovsky, a professor of animal sciences and in the Department of Obstetrics, Gynecology and Women’s Health at the MU School of Medicine, and other collaborators examined zinc-interacting proteins of sperm collected from a fertile male pig at MU’s National Swine Resource and Research Center.

“We found that there were nearly 1,800 proteins in the sperm that were interacting with zinc ions, from which we deduced that zinc must serve as a master-regulator of various processes happening within the sperm to facilitate the recognition and binding of the male and female sex cells, which enables fertilization,” said Zigo, who grew up in Slovakia and studied in Prague, Czech Republic before joining Sutovsky’s lab at MU in 2015.

Zinc keeps sperm in the non-capacitated state in which they cannot fertilize a female egg. However, if the zinc is released from the sperm and the capacitation process occurs prematurely during artificial insemination, a common fertility method used by many livestock farmers to promote reproduction amongst their animals, the sperm cells will ‘burn out’ and die before reaching the egg, so the process is very delicate and time-sensitive.

Sutovsky said that analyzing zinc levels in the sperm of male pigs can help pork farmers make better informed decisions about which pigs would be most useful in the artificial insemination process. Boosting each swine litter by just one piglet would increase the income of U.S. pork farmers by $130 million per year.

“By analyzing the regulatory role zinc plays in sperm cells, we can potentially learn clues about the brief time window for when sperm might have the best chances of successful fertilization,” Zigo said. “Anything we can do to extend that brief window of opportunity for when sperm can successfully fertilize female eggs can positively impact fertility management for animals and potentially human infertility therapy as well.”

Zinc is a vital nutrient for the human body, as zinc deficiencies can cause malnutrition and developmental defects. However, too much zinc can potentially lead to poisoning.

“This research can help us better understand how zinc deficiencies affect infertility in males,” said Sutovsky, who also grew up in Slovakia and studied both animal science and reproductive physiology before coming to MU to further his research in 2001. “For artificial insemination in livestock animals, the zinc-rich seminal fluid typically gets diluted beforehand, so our research shows that premature dilution may trigger premature capacitation, which causes the sperm to burn out and die. Therefore, by supplementing liquid zinc back into the sperm, we can potentially optimize the preparation of sperm for artificial insemination and increase successful fertility outcomes for livestock farmers.”

Sutovsky added that since human nutrition is dependent on food availability, the research can help pig farmers make more food available, which improves human nutrition and decreases food insecurity around the world.

“Better general health leads to better reproductive health, so by boosting fertility efforts and food security, our research helps the circle of life,” Sutovsky said.

In addition to better understanding the role zinc plays as a key regulator of sperm function, the researchers also found that the same proteins involved in biological pathways linked with neurodegenerative diseases, such as Huntington’s disease and Parkinson’s disease, were abundantly populated in the sperm as well.

“The discovery of this unexpected similarity between the brain and reproductive system was surprising, and by setting these foundations, researchers can further investigate these mechanisms going forward,” Zigo said.

As a result, sperm cells could become a non-traditional model to study and manage neurodegenerative diseases.

Zinc is a master-regulator of sperm function associated with binding, motility, and metabolic modulation during porcine sperm capacitation” was recently published in Communications Biology. Funding for the study was provided by the Animal Reproduction Program of the United States Department of Agriculture’s National Institute of Food and Agriculture (USDA NIFA) and the MU College of Agriculture, Food and Natural Resources (CAFNR).