A research team from University California Davis, led by Dr Allison Van Eenennaam, have achieved new advances in cattle embryo breeding technology with the aim of breeding sires that produce 100% same-sex calves.
An Angus-cross calf named Cosmo is the first sex-gene edited calf to be born to this new technology.
The technology has been several years in the making, and it is hoped that if it becomes mainstream in the future, cattle breeders will be able to breed from bulls that sire all male calves in the beef industry and all heifer calves in the dairy industry.
Calf sex
Under normal breeding scenarios, a bull can pass on either X or Y sex chromosomes in his sperm cells, while a cow contains only XX sex chromosomes in her egg cell. Whether a bull passes on either the X (female) or Y (male) chromosome when bred to a cow determines if the calf will be born as a heifer or a bull.
In cattle, the SRY (sex-determining region) gene is responsible for determining male development in a Y chromosome-fertilised embryo, which results in a bull calf at birth.
Using CRISPR gene editing technology, which can cut out and insert or ‘knock-in’ sections of chromosomes, Van Eenennaam and her team initially planned to ‘knock-in’ the SRY gene onto the X chromosome. This would create a bull that sired 100% all male calves. If the calf inherited the Y gene from this sire, the embryo would develop and grow into a typical male bull calf.
If this plan worked, every calf sired by this bull would grow up as bull calves
However, if the calf inherited the X gene from this sire, the SRY gene would override the embryo development and cause the embryo to develop into a bull calf.
Even if the calf was genetically an XX calf, the SRY gene would take control during embryo development and instruct the embryo to develop into a bull calf with all the associated male characteristics. If this plan worked, every calf sired by this bull would grow up as bull calves.
Industry benefits
The benefits of being able to breed all-male or all-female lines of animals would be a major economic boost to farmers. Lines of all female pigs, for example, would eliminate welfare issues in the pig industry such as castration and boar-taint in male pigs, while lines of bull calves in the beef industry would increase efficiency and reduce cost of production on farms.
Bulls typically have 15% better feed conversion efficiency than heifers and enter the food chain at heavier carcase weights. Fewer head of cattle would be needed to produce current beef supply if majority male cattle were reared, which would have economic and environmental benefits.
Successful embryo
After several years of failed attempts to knock-in the SRY gene into the X chromosome, the research team decided to try a different chromosome (Chromosome 17), as the X chromosome was proving too difficult to work with. The experiment worked.
The gene knock-in was successful and the embryo began to develop and grow as normal, before being transferred into a recipient Angus cow to carry the pregnancy.
After nine months of pregnancy, Cosmo was born in early April 2020. Van Eenennaam tested a blood sample from the calf and verified that the SRY gene knock-in had worked successfully. Cosmo’s genetics showed he is an XY calf; inheriting his sire’s Y gene had ensured he would be a bull calf, however, the edited SRY gene was also present on Chromosome 17.
Once Cosmo matures into a yearling, he should in theory sire 50% male calves just like any regular bull when he passes on his Y chromosome, but he should also sire 25% XX heifer calves and 25% XX heifer calves that contain the SRY gene.
All the pressure is now on Cosmo to perform
The real test of the science will be to see if the 25% XX heifer calves with the SRY gene will be born as a bull calf, with all the physical attributes of bulls.
“All the pressure is now on Cosmo to perform. Will his XX offspring that inherit the SRY gene turn out and grow as bulls? If yes, then industry will take the technology and develop it further into commercial use,” Van Eenennaam says.
CRISPR gene editing has been used in the animal industry to breed PERS-resistant pigs in America and TB-resistant cattle in China. Researchers in Florida are currently using the technology to develop heat-stress resistant cattle. In these scenarios, the CRISPR technology simply cuts out the unwanted sections of DNA and the difficult knock-in part of the process was not necessary.
Apart from being early days in the research and development of Cosmo and sex gene editing, USDA regulations will also pose a challenge in future to the technology becoming approved and licensed.
Countries such as Brazil, Argentina and Germany have more favourable regulatory systems and large cattle breeding companies would likely bring the technology to commercial market through these countries.
While sexed semen manipulates the sex of the semen going into the cow at insemination, this new technology changes the genes within the animal to ensure only female or male offspring are born. Cosmo was the first calf born using this approach and his semen should be 75% male. The research was carried out by University California Davis.
A research team from University California Davis, led by Dr Allison Van Eenennaam, have achieved new advances in cattle embryo breeding technology with the aim of breeding sires that produce 100% same-sex calves.
An Angus-cross calf named Cosmo is the first sex-gene edited calf to be born to this new technology.
The technology has been several years in the making, and it is hoped that if it becomes mainstream in the future, cattle breeders will be able to breed from bulls that sire all male calves in the beef industry and all heifer calves in the dairy industry.
Calf sex
Under normal breeding scenarios, a bull can pass on either X or Y sex chromosomes in his sperm cells, while a cow contains only XX sex chromosomes in her egg cell. Whether a bull passes on either the X (female) or Y (male) chromosome when bred to a cow determines if the calf will be born as a heifer or a bull.
In cattle, the SRY (sex-determining region) gene is responsible for determining male development in a Y chromosome-fertilised embryo, which results in a bull calf at birth.
Using CRISPR gene editing technology, which can cut out and insert or ‘knock-in’ sections of chromosomes, Van Eenennaam and her team initially planned to ‘knock-in’ the SRY gene onto the X chromosome. This would create a bull that sired 100% all male calves. If the calf inherited the Y gene from this sire, the embryo would develop and grow into a typical male bull calf.
If this plan worked, every calf sired by this bull would grow up as bull calves
However, if the calf inherited the X gene from this sire, the SRY gene would override the embryo development and cause the embryo to develop into a bull calf.
Even if the calf was genetically an XX calf, the SRY gene would take control during embryo development and instruct the embryo to develop into a bull calf with all the associated male characteristics. If this plan worked, every calf sired by this bull would grow up as bull calves.
Industry benefits
The benefits of being able to breed all-male or all-female lines of animals would be a major economic boost to farmers. Lines of all female pigs, for example, would eliminate welfare issues in the pig industry such as castration and boar-taint in male pigs, while lines of bull calves in the beef industry would increase efficiency and reduce cost of production on farms.
Bulls typically have 15% better feed conversion efficiency than heifers and enter the food chain at heavier carcase weights. Fewer head of cattle would be needed to produce current beef supply if majority male cattle were reared, which would have economic and environmental benefits.
Successful embryo
After several years of failed attempts to knock-in the SRY gene into the X chromosome, the research team decided to try a different chromosome (Chromosome 17), as the X chromosome was proving too difficult to work with. The experiment worked.
The gene knock-in was successful and the embryo began to develop and grow as normal, before being transferred into a recipient Angus cow to carry the pregnancy.
After nine months of pregnancy, Cosmo was born in early April 2020. Van Eenennaam tested a blood sample from the calf and verified that the SRY gene knock-in had worked successfully. Cosmo’s genetics showed he is an XY calf; inheriting his sire’s Y gene had ensured he would be a bull calf, however, the edited SRY gene was also present on Chromosome 17.
Once Cosmo matures into a yearling, he should in theory sire 50% male calves just like any regular bull when he passes on his Y chromosome, but he should also sire 25% XX heifer calves and 25% XX heifer calves that contain the SRY gene.
All the pressure is now on Cosmo to perform
The real test of the science will be to see if the 25% XX heifer calves with the SRY gene will be born as a bull calf, with all the physical attributes of bulls.
“All the pressure is now on Cosmo to perform. Will his XX offspring that inherit the SRY gene turn out and grow as bulls? If yes, then industry will take the technology and develop it further into commercial use,” Van Eenennaam says.
CRISPR gene editing has been used in the animal industry to breed PERS-resistant pigs in America and TB-resistant cattle in China. Researchers in Florida are currently using the technology to develop heat-stress resistant cattle. In these scenarios, the CRISPR technology simply cuts out the unwanted sections of DNA and the difficult knock-in part of the process was not necessary.
Apart from being early days in the research and development of Cosmo and sex gene editing, USDA regulations will also pose a challenge in future to the technology becoming approved and licensed.
Countries such as Brazil, Argentina and Germany have more favourable regulatory systems and large cattle breeding companies would likely bring the technology to commercial market through these countries.
While sexed semen manipulates the sex of the semen going into the cow at insemination, this new technology changes the genes within the animal to ensure only female or male offspring are born. Cosmo was the first calf born using this approach and his semen should be 75% male. The research was carried out by University California Davis. 
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