In the early 20th century, major scientific discoveries were a dime a dozen. Continental drift, the Milky Way galaxy, penicillin, genetics – the mysteries of the universe kept toppling like dominoes. “They kind of got to pick the low-hanging fruit,” says Dr. Bret Taylor, an animal scientist at the U.S. Sheep Experiment Station in Dubois, Idaho. “Precision science – that’s what we’re in now.”
Wingate’s Dr. Alison Brown, with the help of her colleague Dr. Erika Niland, Taylor and multiple Wingate students, has been working on some very specific precision science that has an opportunity to refine sheep producers’ thinking, and possibly even affect the way we look at disease in humans.
This summer, Brown, Niland, Taylor and another U.S. Sheep Experiment Station colleague, Natalie Pierce, published a paper showing that “microchimerism” – the presence of male DNA in a female – can occur in sheep. Brown, the lead author, discovered that male fetal cells are able to cross over to the mother sheep and remain there after pregnancy has ended.
In humans, microchimerism involving cell transfer from a male fetus has been studied in women for several years, and male fetal cells can remain in the mother’s body after pregnancy ends, sometimes for decades. Fetal cells can also transfer from older to younger siblings or from one generation to another. Scientists are not sure whether fetal-cell transfer causes harm, but, by coincidence, male fetal cells have been found in tissues of women who have autoimmune diseases or brain tumors.
Down the road, it’s possible that the discovery by the Wingate professors could make it easier to study the phenomenon in sheep in order to help discover its effects in humans. It could also eventually change how sheep producers do business, but even if it does neither of these things, it’s still a major discovery of basic science in domestic animals. “No one knew if male fetal cells could move into solid tissues of a mother sheep, such as the brain, let alone remain there over time,” Brown says. “We are the first ones to say, ‘Yes they can.’”
Brown has been studying sheep reproduction for years, previously having disproven earlier research suggesting that ewes with twin brothers were less fertile. In 2016, she gave a “distinguished alumni lecture” and the commencement speech at her doctoral alma mater, West Virginia University’s Davis College of Agriculture, Natural Resources and Design. Afterward, a clinical professor suggested that she look into fetal microchimerism in sheep.
“Once I spoke to Bret about it, he was very supportive and suggested that this could have a big impact on the sheep industry,” Brown says.
Brown enlisted the help of Niland, associate professor of biology and an expert at examining tissue at the molecular level. Niland and Brown perfected a technique for isolating DNA to see whether any solid tissues collected from maternal sheep contained a Y chromosome.
Using Real-Time PCR (polymerase chain reaction) to copy DNA is an art as much as a science. The Wingate professors heated up samples so the DNA would pull apart into single strands, then cooled them down to get “primers” (short DNA strands) to attach to the DNA. Finally, they had to heat them up again just enough for the polymerase enzyme to replicate the DNA fully.
The pair then ran the DNA on a gel to visualize what they had isolated. As this study tries to answer more questions, they’ll be using a fluorescent probe Niland developed to make them even more confident in their results.
It took many months of replicating the process before they were confident in their techniques and were certain their samples were not becoming contaminated. Students working with Brown and Niland saw the realities of science, in that, most of the time, experiments do not go as planned, and researchers have to step back, reevaluate, and start again.
“You basically just have to troubleshoot and keep the amount of replicants high, ensure that you are repeating the experiment and everything is correct, because you want to make sure you are, in fact, identifying those cells, that Y chromosome, and not anything else,” Niland says.
In the end, they were able to conclusively prove that fetal cells from male sheep were finding their way into the ewes.
Meaningful research, with student help
The finding was an “important discovery,” Brown admits, but there’s still a long way to go before it translates into actionable information for the industry. The next step is to quantify the fetal microchimerism in ewes and then eventually determine whether a relationship exists between fetal cell transfer and a ewe’s well-being. Ultimately, the research could get to the point where the findings serve as a guide to sheep producers, making their industry more productive. The goal is to make the ewes more fertile: If they can produce more offspring in their lifetime, the industry works more efficiently, saving money and energy.
“Whenever we look at the production of our foods, whether it’s animals or crops or fruit trees, it is about efficiency,” Taylor says. “The longer an animal stays reproductively sound, the more our efficiency of production improves.”
But he believes the benefits could go beyond the ranges of the Mountain West.
“There is a lot of anecdotal evidence out there that microchimerism, at least in humans, can be linked to a number of later-age diseases and problems in females,” Taylor says. “Through her work, I think Alison will be able to propose sheep as a possible model to study microchimerism, to aid in human medicine and research and study to understand if these male cells transfer and, if they transfer, where they are likely to show up and reside for a long time.”
The research is also of huge benefit to a select group of Wingate biology students. Since beginning the study, Brown has drafted in five students to travel with her to Idaho to collect tissue samples and work with a variety of USDA scientists and staff.
“The students get the full exposure here,” Taylor says. “A full molecular lab. They’re processing samples, extracting DNA, looking for specific gene sets or snips, or whatever they’re chasing. They find out how to handle an animal, and how to collect a sample in an animal that doesn’t injure the animal. They also work with other crews and technicians to see what they’re doing.”
Taylor, who works with more than a dozen universities, most of them large land-grant institutions, says Brown forges closer relationships with her students than most.
“They’re always eager to please Alison,” he says. “Alison can clearly present a goal, and I think they want to work toward achieving that goal, because they want her positive congratulations.”
And in this case, they also get to say that they worked on some groundbreaking research.
“This is a big deal,” Brown says. “I’ve had five undergraduates work on this project, and I look forward to working with many more.”
In fact, getting students quality research opportunities is why she studies sheep in the first place.
“Oh yeah! Absolutely,” she says. “But at the same time we’re making some pretty big discoveries along the way.”
Oct. 11, 2021