Developments in molecular biology, immunology and genetic engineering have given new dimensions to research on farm animal production. The LSU AgCenter’s Reproductive Biology Center is recognized worldwide as a leader in assisted reproductive technologies for use in livestock improvement, biomedical applications, and propagation of exotic and endangered animal species.
Watch a 2-minute video about the Reproductive Biology Center.The world’s first cloned transgenic goats were born as part of a research program conducted by the LSU AgCenter and Genzyme Transgenic Corp. – now GTC Biotherapeutics. Although the goats made their appearance in 1998 at the Genzyme farm in Massachusetts, much of the research that developed them was done at the AgCenter’s Reproductive Biology Center in St. Gabriel under the direction of Robert Godke, Boyd Professor in the School of Animal Sciences and internationally known for his research in assisted reproductive technologies in animals and now retired.
The milk from those goats produces a drug – ATryn (Antithrombin [Recombinant]). The human protein antithrombin inhibits clotting. In February 2009, GTC Biotherapeutics and Ovation Pharmaceuticals announced that the U.S. Food and Drug Administration approved ATryn for hereditary antighrombin-deficient patients. People with hereditary antithrombin deficiency are at increased risk for such problems as pulmonary embolism and deep vein thrombosis.
The LSU AgCenter has been in the business of helping farm animals reproduce more efficiently since the early 1980s. In addition to the cloned goats, the AgCenter produced the world’s first calf from an in vitro fertilized embryo where the egg was harvested from a live pregnant cow, for example, and the first cloned goats to produce a human heart medication in their milk.
The research focus at the Reproductive Biology Center includes gamete technology and manipulation with emphasis on embryo biotechnology. Gametes are the sperm and eggs (ova) that carry single sets of unpaired chromosomes. When they come together, they form zygotes and then embryos that have a full complement of chromosomes contributed by both parents.
The Reproductive Biology Center works with four species – cattle, goats, swine and horses. The focus on cattle and goats is for breeding applications to improve meat and milk production while all four species are used in biomedical research. In addition to cloning, researchers have been focusing on transgenic animal models – those with specific genes introduced from other sources – that can produce important pharmaceuticals and transfer that ability to their offspring.
AgCenter researchers were first in the world to produce in vitro fertilization-derived pregnancies and live offspring in beef cattle with cattle epididymal sperm. To save germplasm from deceased bulls, scientists saved epididymal sperm by storing it in the testes at 39 degrees for 24 hours. Then they used a “test tube” fertilization (in vitro fertilization) procedure that produced viable embryos and living offspring from 46 percent of the beef females that received the embryos.
“With this capability, cattle producers will now have to opportunity to harvest germplasm – testicular sperm – from a recently deceased genetically valuable bull or from an injured breeding bull no longer able to mate,” Godke said. “Cattle producers have requested this technology from scientists for decades.”
AgCenter researchers have successfully developed methods to harvest oocytes (eggs) from cattle, horses, goats and sows using transvaginal ultrasound-guided procedures. Read Oocyte Aspiration for In Vitro Embryo Production in Farm Animals.
Harvesting oocytes from live farm animals on multiple occasions in a noninvasive manner is an important breakthrough for test tube fertilization. Read Cattlemen Pleased with Cloned Calf, Thanks to LSU AgCenter Research and Graduate Student Produces First Cloned Cow From Frozen Egg.
Read Animal Biotechnology and the Future.
“Producing one or two extra calves per year from breeding herd females will increase the producer’s annual calf crop,” Godke said. “With the potential to increase the efficiency of animal production, this technology is now being implemented by progressive cattle producers.”
One of the focus areas of Godke’s research has shifted to white-tailed deer. Hunters shoot the big ones (bucks), and smaller male deer are left to repopulate, which could lead to smaller animals in the future. Because hunting is an important economic factor in Louisiana, Godke and his associates have been harvesting the testes from bucks hunters have shot and freezing the epididial sperm. They’ve found that the sperm is viable and can be used to artificially inseminate female deer to help maintain a vibrant deer population.
Other applications for human health
Animal scientists have been working with embryo manipulation and nuclear transfer for years. These techniques have many applications in improving animal production in addition to their use to advance basic biotechnology. Now, animal science is moving toward a larger arena that includes biomedical application and work with endangered species – not just production animals.
In other research at the Reproductive Biology Center, Ken Bondioli, associate professor in the School of Animal Sciences, is looking at transgenic pigs as models for diagnosing and treating Alzheimer’s disease in people. He says current rodent models show a number of genes associated with development of the disease, but they don’t develop the full nature of the disease as it appears in humans. Other animals, however, have brain structures more like humans’ – including the pig.
Researchers are trying to express in pigs a mutation of the human protein associated with the high incidence of early-onset Alzheimer’s disease, which can be inheritable. All kinds of things happen during aging in people, so researchers are trying to identify what causes the disease because age is a problem in diagnosis.
The AgCenter researchers also are working with LSU Health Science Center to identify molecular markers associated with Alzheimer’s disease. The model needs to identify changes early in life, Bondioli says. But the result could be useful in diagnosis and evaluating treatments.
In other research, Bondioli is working with a company that is interested in developing human protein in animals, similar to Godke’s work with goats. Animals that chew cud produce a large amount of saliva, and proteins that appear in saliva influence digestion and pH.
Developing nutritionally important proteins in animal saliva has had some small success. The potential application includes a wide platform to deliver a protein to the digestive system through saliva, which could benefit animal production and improve feed efficiency.
Researchers have been working on how they can cause cells to reproduce and express themselves as different body cell types. It may be possible, for example, to develop cells that could regenerate spinal cords or treat Parkinson’s disease or Alzheimer’s disease. Researchers might also be able to develop cells that could replace cardiac muscles or make cartilage to repair joints or replace bones as well as regenerate a diseased pancreas or liver.
“There’s potential for cell-based therapy for regeneration, repair or replacement for any organ,” Bondioli said. “The potential is limited by imagination; reality is limited by biology, which is where we’re trying to identify answers. Most of these questions will be answered by developing animal models.”
Biotechnology companies now produce new recombinant DNA proteins to treat various viral diseases in farm animals. An example is a class of natural antiviral proteins called interferons used to treat calf scours and various respiratory diseases, such as shipping fever in cattle.
Beef cow productivity
Glen Gentry, assistant professor, has a project to research leptin, a hormone derived from adipose tissue, and how it relates to reproductive efficiency in farm animals.
Gentry said puberty occurs when an animal becomes reproductively competent based on weight and age – generally 65 percent of mature body size. He said researchers believe leptin serves as a trigger mechanism that is involved in the process. So he’s looking at heifers and 2-year-old beef cows to see if leptin can be used in predicting success rates in pregnancy.
“A two-year-old cow often has difficulty becoming pregnant because she is using her energy for growing and for making milk for a calf,” Gentry said. “A healthy cow needs to maintain body mass.”
The results of this research will provide another measure producers can use to select future cows for their herds. It would be another animal selection tool. The more parameters producers can measure, the better control they can have of the reproductive efficiency of their herds.
Collecting embryos from top-quality cows allows producers to get more calves from these animals. Normally, cows will produce only one potentially viable embryo that attaches to the uterus and produces a calf. But if producers can harvest six to eight embryos from one donor cow at a time and freeze them until suitable surrogate mothers are available to produce the offspring, they can increase the productivity from the top cows in their herds.
Usually a donor cow’s embryos can be harvested three times in a year – yielding a potential of 18 or more calves per donor cow each year. This allows top bulls paired with outstanding cows to produce an excellent crop of calves each year. Frozen embryos usually produce slightly lower pregnancy rates than fresh embryos. Researchers at the center are using a laser attached to a microscope to cut “notches” in the frozen-thawed embryos in an effort to stimulate “hatching” of the embryo and increase the pregnancy rates of transferred embryos.
The Reproductive Biology Center has accreditation from the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. The accreditation certifies this LSU AgCenter research unit, which includes its Embryo Biotechnology Laboratory, is providing the highest-quality care of the animals used in its research program and is accountable in maintaining a standard of excellence.
In addition to funding from the AgCenter, the Reproductive Biology Center has received grants from the U.S. Department of Agriculture, National Institutes of Health, the Louisiana State Board of Regents and private companies.
“The infrastructure and capability to do a multitude of types of research with high potential to bring in the outside funding necessary for this research to be completed,” Gentry said.
The LSU AgCenter is one of 11 institutions of higher education in the Louisiana State University System. Headquartered in Baton Rouge, it provides educational services in every parish and conducts research that contributes to the economic development of the state. The LSU AgCenter does not grant degrees nor benefit from tuition increases. The LSU AgCenter plays an integral role in supporting agricultural industries, enhancing the environment and improving the quality of life through its 4-H youth, family and community programs.
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