Zinc plays a key role in promoting male fertility, according to findings by researchers at the University of Missouri (MU). The discovery has implications for improved in vitro fertilization and artificial insemination (AI) in livestock and for human infertility diagnostics and therapies.
The findings of Dr. Peter Sutovsky, a professor of animal science in MU’s College of Agriculture, Food and Natural Resources, and doctoral student Karl Kerns were published recently in Nature Communications. Coauthors of thearticle, “Zinc ion flux during mammalian sperm capacitation,” were Michal Zigo, Erma Z. Drobnis and Miriam Sutovsky, also of MU.
[inline_image file=”b49375170ad1678cb78c422dc6ee00f9.jpg” caption=”Peter Sutovsky (on left) and Karl Kerns found that zinc plays a key role in promoting fertility in males, a discovery that has implications for improved in vitro fertilization and artificial insemination in livestock, and for human infertility diagnostics and therapies.”]
Kerns, whose area of study is animal science with an emphasis in reproductive physiology, told WLJ the study was set in motion by a new biological phenomenon that’s been described as a “zinc spark” on the oocyte (egg or female) side. He said that occurs shortly after fertilization, so the role of zinc on the oocyte side and post-fertilization has been well described. However, he said, “What zinc does on the male side specifically within sperm before it meets the egg hasn’t been described, so we wanted to complete the biological story per se.” He added, “We know that zinc is very important for male fertility, but the exact molecular mechanisms weren’t understood, so that’s what we wanted to dig into.”
The study involved pigs, cattle and humans. Sutovsky noted, “Zinc is linked directly with fertility. We have known that giving males zinc supplements—whether pigs or humans—improves fertility. Now we know that analyzing zinc signatures can help us quickly evaluate the fertilizing potential and quality of sperm.”
An article by MU discussing the study explained that for some time scientists have struggled to understand what regulates sperm “capacitation,” the vital physiological process sperm must undergo to become capable of fertilizing an egg cell. Sutovsky and Kerns used a state-of-the-art image-based flow cytometer—which can take images of up to 2,000 cells per second and track biomarkers such as zinc with fluorescent dyes—to monitor zinc localization during various stages of capacitation in sperm cells. They found that zinc ions exert significant control over capacitation beyond merely enabling the process, in that the ion can prevent and even reverse the capacitation process in some cases. This also occurs when an egg has already been fertilized and must defend against another fertilization. Various stages of bull semen are illustrated in Figure 1.
[inline_image file=”a5118b49cb83e7819b30dc1fe200103f.jpg” caption=”Figure 1.Researchers identified four distinct types of sperm zinc signatures conserved across boar, bull (Fig. 1 e–h), and human spermatozoa: high Zn2+ presence in the sperm head and whole-sperm tail (signature 1; Fig. 1 e), medium-level (based on relative intensity of fluorescence in FlowSight measurements) Zn2+ presence in both the sperm head and sperm tail midpiece (signature 2, spermatozoa undergoing capacitation; Fig. 1 f), Zn2+ presence in the midpiece only (signature 3/capacitated state signature in spermatozoa that underwent capacitation and may be dying; Fig. 1 g), and no Zn2+ presence (signature 4, spermatozoa with compromised/remodeled plasma membrane; Fig. 1 h). MU College of Agriculture, Food and Natural Resources.”]
Asked if this may impact zinc in feed supplements or open the door for additional studies, Kerns said it could create opportunities for both additional feed and fertility trials. He noted that in fertility trials scientists should look at how zinc can be used as a predictor of fertility. “Then we can perhaps change some of our artificial insemination techniques; whether it’s timing or something else. We know some bulls don’t do well in timed AI. This might give us a better idea of which bulls are good at timed AI and which bulls aren’t good at timed AI, as well as how we can change those protocols.”
Using the technology to identify zinc signatures and subsequent information as predictor of fertility could aid the AI process when determining the level of semen dilution. Kerns said, “Once we know the exact zinc signature and how that changes within each bull that will then dictate how many sperm are needed per AI dose.”
Kerns said there are two options when looking for the zinc signature: a quick test; or a longer four-hour test. He said the longer test adds another level of safeguarding the future fertility and looks at the ability to change after in vitro capacitation, which, he said, is advantageous. But he said it depends on each situation.
He said the test could possibly be able to identify difference in male fertility between breeds of cattle. “That’s another exciting area to look at. Really, this is almost a gold mine, per se of a new era in male fertility, whether that be boar, bull or human. So, looking at the variability and differences between breeds, by all means is something that needs explored in the next decade for sure, or sooner.”
Length of study
Kerns told WLJ initial results in the study to identify the zinc signatures were identified pretty fast—within two to three months. After that an additional year was needed to understand how it chelated throughout capacitation and some of the molecular mechanisms. Finally, Kerns said an additional year was needed to complete the peer review process.
As noted, Kerns said additional areas need to be explored within the next 10 years or sooner. Asked if timetables are sometimes difficult to meet when dealing with science as new discoveries can often take researchers in new directions, he responded, “The fun thing about science is when you are open to letting the science take you where it is and not being biased, you’re open to what the science uncovers for you. So, we’re always in tune with that and what we are trying to do—studies at the molecular level—and that being translatable to the livestock industry.”
Human implications
While the findings are exciting and of interest to livestock producers there are also implications for human reproduction. Infertility affects about 20 percent of the human population. Kerns said, while a common problem, it is a topic often viewed as taboo to talk about in society. He said the National Institutes of Health and Centers for Disease Control and Prevention believe that two-thirds of that is directly or indirectly related to the male, “but we don’t have diagnostic methods to exactly elucidate that and to decide if it is a male or female in the relationship.”
Preliminary studies with humans were conducted with semen data from the University of Missouri Children’s Hospital. Kerns said his team is interested in following up with a larger trial and is talking with potential collaborators.
Next steps for livestock
Asked about immediate implications for the livestock industry, Kerns said, “I think one of the quickest things to implement right away is starting to do diagnostics on every bull ejaculate to see what their zinc signature is. Then tying that to future fertility. It would be nice to see that being used as a diagnostic mechanism within bull studs.”
Kerns explained that he grew up on a farm, saying, “I am very passionate about making sure that we can help the U.S. farm producers out and creating better results for the farms. We’re looking at how we can increase what the farmers do at the farm level.” — Rae Price, WLJ editor
