Gene-edited livestock successfully fertilized ‘surrogate cyrs’

For the first time, scientists have created pigs, goats and cattle that can serve as viable “surrogate cyrs,” male animals that only produce sperm with the genetic characteristics of donor animals.

Published in Advance, Proceedings of the National Academy of Sciences September 14, may accelerate the spread of desirable characteristics in livestock and improve food production for a growing global population. It will enable breeders in remote areas better access to the genetic material of elite animals from other parts of the world and allow more precision breeding in animals like goats where artificial insemination is difficult to use.

“With the help of this technology, we can better propagate desirable traits and improve the efficiency of food production. This could have a major impact in eliminating food insecurity worldwide,” said John Otley, a reproductive biologist at WSU’s College of Veterinary Medicine. “If we can deal with this genetically, it means less water, less food and less antibiotics we have to put in animals.”

A research team led by Ottley used animal editing tool, CRISPR-K9, to harden the male reproductive gene in the animal embryo, which will be raised to become a surrogate serum. Male animals were then born sterile, but researchers began producing sperm after transplanting donor animal stem cells into their tests. Sperm, made by sperm, contain only the genetic material of selected donor animals. The gene-acquisition process employed in this study seeks to alter the species of animals that can occur naturally, such as infertility.

The study is the result of six years of collaborative work between researchers at WSU, Utah State University, the University of Maryland and the Roslin Institute at the University of Edinburgh in the UK.

The researchers used CRISPR-Cas9 to produce mice, pigs, goats and cattle that lacked a gene called NNOS2 that is specific to male fertility. Male animals became sterile but otherwise healthy, so when they got stem cells that produced sperm from other animals, they began to produce sperm from donor cells.

Active donor semen was confirmed to surrogate cyrs. Surrogate mice were the offspring of healthy offspring who carried the genes of donor mice. Large animals have not yet been bred. Ottley’s lab is improving the stem cell transplantation process before taking the next step.

The study provides powerful evidence of imagination, said Bruce Whitlow, a professor at the Roselyn Institute.

“This shows the world that this technology is real. It can be used,” Whitela said. “We have to go into it now to feed our growing population and it’s best to know how to use it productively.”

The latest step in animal husbandry

Scientists have been looking for ways to create surrogate sirens for decades to overcome the limitations of selective breeding and artificial insemination, tools that require either animal proximity or strict control of their movement – and in many cases, both.

Artificial insemination is common in dairy cattle that are always limited so it is relatively easy to control their breeding behavior, but this process is rarely used with beef cattle that need to move freely to feed. For pigs, the animals still need to be close in the process because the pig’s sperm does not stay cold. In goats, artificial insemination is quite challenging and may require a surgical procedure.

Surrogate Sawyer technology can solve those problems because surrogates deliver donor genetic material naturally – through normal reproduction. This allows pastoralists and ranchers to interact with their animals in general on a range or area. Stable donor semen or the surrogate animal itself can migrate to different locations so donors and surrogates do not need to be close to each other. In addition, female NNOS2 knockout animals remain fertile, as the gene only affects male reproduction – and effectively sterilized males to use it as a surrogate sergeant.

Irina Polejaeva, a professor at Utah State University, said the technology has great potential in supplying food to locations in the developing world, where pastoralists still have to rely on selective breeding to improve their stock.

“Goats are the number one source of protein in many developing countries,” Polejaeva said. “This technology can allow rapid propagation of specific qualities in goat goats, whether they are disease resistant, tolerate more heat or have better meat quality.”

Surrogate Cyrus technology could also open up a new option for the genetic conservation of endangered species, the declining number of which separates animal communities from each other, limiting their genetic diversity.

Assumptions and policy barriers

No benefit of surrogacy can be realized without changing government regulations and the current landscape of public perception.

Although technologically advanced enough for commercialization, offspring are not gene-edited, gene-edited surrogate sarees cannot be used in food chains anywhere in the world under current regulations. Ottley said that partly because of these misconceptions, gene acquisition is similar to controversial gene manipulation. Gene editing involves mutations in species that can occur naturally. It does not bind to the DNA of different species.

Otley realized that there was still a lot of work to be done outside of Labost and recently joined the National Task Force on Gene Editing in Livestock to give researchers, industry representatives, biostatists and policy makers a way forward for technology.

“Even if all science is finished, the pace at which this can be taken into account in livestock production anywhere in the world could be influenced by social acceptance and federal policy,” Otley said. “By working with policy makers and the public, we can help provide information to the public assuring them that this science is not at risk due to other methods.”