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Stem cell breakthrough allows male livestock to serve as 'surrogate sires'

A breakthrough in stem cell research allowed scientists to create ‘surrogate sires’ that produce sperm with the genetic traits of a donor animal.

So far the new technique has been used to create pigs, goats and cattle with the sole purpose of producing sperm with the DNA of another male. 

Researchers from Washington State University say it could one day solve starvation for the world’s growing population – or save species from extinction.

Surrogate ‘super dads’ will dramatically boost the quality of livestock by allowing farmers to select the strongest DNA of each breed to reproduce. 

In experiments, mice have already fathered healthy offspring who carried the genes of donor rodents – larger animals carrying donor sperm have yet to breed. 

Project leader Professor Jon Oatley, said by selecting DNA farmers can get better dissemination of desirable traits and improve the efficiency of food production.

This is a gene-edited surrogate bull. It can't produce its own genetic offspring but in future its sperm will carry the genetic material of another bull and will pass it on to cows

This is a gene-edited surrogate bull. It can’t produce its own genetic offspring but in future its sperm will carry the genetic material of another bull and will pass it on to cows

The new technique, developed by Oatley and colleagues, could have a ‘major impact’ on addressing food insecurities around the world.

TECHNIQUE ALLOWS ANIMALS TO REPRODUCE THE NATURAL WAY

The new technique involves switching off the NANOS2 gene in the embryo of a target animal.

This ‘switches off’ the ability for males of the species to reproduce.

When they can reproduce – stem cells from a donor animal are transplanted into their testes.   

Then when they reproduce they only pass on the transplanted DNA. 

Artificial insemination is rarely used with beef cattle who need to roam freely to feed and in pigs the animals have to be nearby as their sperm doesn’t last long. 

Surrogates deliver the donor genetic material the natural way – through normal reproduction.

This enables farmers to let their animals interact normally. 

Donors and surrogates do not need to be near each other since either frozen sperm or the animal itself can be shipped to different places. 

‘We can tackle this genetically, then that means less water, less feed and fewer antibiotics we have to put into the animals,’ Oatley of Washington State said.

His researchers included colleagues at Edinburgh University’s Roslin Institute, famous for Dolly the Sheep – the world’s first cloned mammal.

They used a gene editing (GE) tool called CRISPR-Cas9 which has been described as a pair of ‘molecular scissors’ – snipping DNA using a harmless virus.

Unlike genetic modification, nothing is added from another species – it is just the selection of the best DNA from other members of the same species.  

Oatley and colleagues removed a male fertility gene called NANOS2 in the embryos of pigs, goats, cattle and mice that would be raised as ‘surrogate sires’.

These mammals then grew up sterile, but otherwise healthy. They began producing sperm after stem cells from donor animals were transplanted into their testes.

It held only the genetic material of the selected creatures – nothing from the surrogate sire.

The groundbreaking procedure only seeks to bring about changes that could occur naturally – such as infertility, according to the transatlantic team.

Oatley’s lab is now refining the system before the next step – getting offspring from the surrogate pigs, goats and cattle. They will not be their own – but the donor’s.

Dr Harry Leitch, an expert in genetics and reproduction from Imperial College London, not involved in the study, said the research is an important step forward.

‘The next step in pigs and goats will be to demonstrate that this sperm is functional – meaning that it can fertilise an egg and make healthy offspring,’ he said. 

Experts have been searching for a way to create surrogate sires for decades to overcome selective breeding and artificial insemination.

The latter is common in dairy cattle who are often confined and so their reproductive behaviour is relatively easy to control, the team explained.

Artificial insemination is rarely used with beef cattle who need to roam freely to feed and in pigs the animals have to be nearby as their sperm doesn’t last long. 

Surrogates deliver the donor genetic material the natural way – through normal reproduction – enabling farmers to let their animals interact normally. 

Donors and surrogates do not need to be near each other since either frozen sperm or the animal itself can be shipped to different places.

Goats are particularly difficult to artificially inseminate but this new technique allows the healthiest males to pass their genetic material to animals via a donor sire

Goats are particularly difficult to artificially inseminate but this new technique allows the healthiest males to pass their genetic material to animals via a donor sire

Washington State University reproductive biologist Jon Oatley feeds a goat 'surrogate sire'

Washington State University reproductive biologist Jon Oatley feeds a goat ‘surrogate sire’

The change in the genetic material doesn’t render females infertile – it only affects male fertility – so a girl interacting with a donor sire could still have fertile girls. 

It has great potential to help food supply in places in the developing world where herders have to rely on selective breeding to improve their stock.

Co-author Prof Irina Polejaeva, of Utah State University, said: ‘Goats are the number one source of protein in a lot of developing countries.

‘This technology could allow faster dissemination of specific traits in goats, whether it’s disease resistance, greater heat tolerance or better meat quality.’ 

The technology also opens the door to genetic conservation of endangered species whose dwindling numbers leave animals isolated – limiting their genetic diversity. 

Prof Oatley added: ‘Even if all science is finished, the speed at which this can be put into action in livestock production anywhere in the world is going to be influenced by societal acceptance and federal policy.

‘By working with policymakers and the public, we can help to provide information assuring the public that this science does not carry the risks that other methods do.’

The findings have been published in the journal Proceedings of the National Academy of Sciences.

EPIGENETICS: THE SCIENCE OF ALTERING EXPRESSIONS OF CERTAIN GENES

Epigenetics is a field of molecular science which involves altering the expression of certain genes. 

It is defined as: ‘The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.’

Instead of changing the genes present in a living thing, it changes which of its genes are ‘turned on’. 

Although it is the genetic code which forms the foundations for every living organism, it is the combination of activated genes which defines it.

This gene expression can be complex or simple and can control a wide range of features. 

As some features and behaviours are controlled by single genes, these can be easily altered by turning this gene off, for example. 

Some genes inhibit growth and limit cell proliferation, by deactivating these genes things can be grown which do not have the same natural limitations as before.  

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