Imagine a future where you could pick the sex of your calves. Most commercial ranchers might opt for all male calves since steers bring more at the auction yard. But aside from sexed semen, that future is little more than science fiction.
Dr. Alison Van Eenennaam is working on a project that might make that possible future a fact.
Van Eenennaam—a Cooperative Extension specialist in animal genomics and biotechnology at University of California, Davis—talked to WLJ last week about her “Boys Only” project. The project is in very early stages and seeks to determine if the genetic editing tool CRISPR can be used to create bulls that would produce all-male offspring.
“We’re trying to just produce the more efficient gender,” she said, noting that heifers are often discounted compared to steers in the beef industry. “That’s really what the project is about.”
Sex Genetics 101
Before jumping into the details of Van Eenennaam’s project, here’s a brief refresher on the genetics of sex.
An individual’s genetic sex is determined by their chromosomes. In mammals, females’ sex chromosomes are XX and males’ are XY. When producing gametes—eggs in females and sperm in males—an animal contributes half of its genetic information to a potential offspring.
Female mammals’ eggs will always contain X chromosomes, since that’s all they have to give. Males can offer both X and Y chromosomes, however. Some sperm carry the X chromosome, and some sperm carry the Y chromosome. This means the male’s genetic contribution determines the sex of the offspring in mammals.
This is genetic sex. However, there are other things that control an individual’s phenotypic sex—the outward physical characteristics. One such gene is “SRY.”
A male by any other genes
“Normally, in mammals, there’s a gene called SRY, which determines you being male,” Van Eenennaam explained. The gene is naturally found on the Y chromosome and codes for a protein involved with male sexual development. This includes the presence of a penis, testicles, the production of testosterone, and other physically male characteristics.
“If you move that gene onto the X chromosome of a bull, he will produce sperm that have the Y chromosome that just become normal males, and then you’ll have the X chromosome carrying the SRY gene,” Van Eenennaam explained.
“When an animal inherits that, the SRY gene will trigger the male pathway even though the animal is XX. So, she will become phenotypically male. In other words, she will appear to be male.”
These XX males would be sterile, but Van Eenennaam said that’s not an issue.
“She would look like a male but wouldn’t form fertile sperm. So, she would be infertile, but no one cares if you are producing a steer—steers aren’t fertile either.”
Industry impetus
“There’s a case to be made for raising the gender that’s most optimized for a particular production system,” Van Eenennaam explained. She added that a bull that was edited to produce only male offspring “would be a more efficient terminal sire for the beef industry because, on average, steers are somewhere around 10 percent more efficient than heifers.”
In recent auction reports, 4-weight feeder heifer calves have seen a $10-30/cwt. discount compared to same-weight steer calves. The discount drops to about $10 on 7-weight feeder heifers compared to same-weight feeder steers.
Breeding using artificial insemination (AI) with sexed semen could be used to achieve the same ends. However, the semen-sexing process can reduce the viability of sperm and can decrease conception rates. The infrastructure needs of breeding via AI is also a challenge to many commercial ranchers.
“But if a bull could go out and achieve the same end, then why not?” Van Eenennaam asked rhetorically.
Bulls edited to have the SRY gene on their X chromosome would be “a genetic dead-end,” Van Eenennaam said.
“The only ones who could pass it on would be the females, but they are males and they are infertile, so that’s the end of the line. You would have to keep making the bulls every generation.”
The distant horizon
All of this is hypothetical right now. Even the possibility is years away.
“First of all, we have to produce the animals and make sure they’re all boys,” said Van Eenennaam.
“We have to get the cell line cloned and those animals have to grow, they have to mature, then we collect semen, and then we inseminate cows. So, we’re at least two-and-a-half years away from testing our hypothesis that [the bulls’ offspring] will be all male.”
The Food and Drug Administration (FDA) regulations on gene-edited animals also means the project could be bogged down for years.
The FDA released a draft guidance in January 2017 regulating gene-edited food animals and their offspring as drugs under the Federal Food, Drug, and Cosmetic Act. Such regulation usually involves years of tests before a product can reach the market.
“If it’s [regulated as] a drug, then you’re going to have to go through a multi-generational drug approval process,” Van Eenennaam explained. “You have to show it safe for the animal, you have to show it safe for humans, you have to show it’s transmitted and that it works as advertised and do all of the type of testing you would have to do for a dog wormer, which makes no sense.”
Van Eenennaam expressed frustration over the FDA position on regulating gene-edited animals as drugs, opining that regulations are to protect the public from risk and regulatory scrutiny should be comparable to risk.
“In this case, what is the phenotype? Male. … Have we ever eaten males? Yes, we do that pretty often. So, what are we regulating? What’s the unique risk? I have a hard time coming up with one.”
Though Van Eenennaam’s project seeks to genetically edit bulls to intentionally have the SRY gene on their X chromosomes, the condition does occur naturally as a genetic abnormality.
“We’ve seen this condition in humans. We’ve seen this condition in horses. We’ve seen this condition in mice. But we’ve never seen it in cattle.”
In humans, the SRY gene showing up on the X chromosome is a condition called “46 XX testicular disorder of sex development.” According to the U.S. National Library of Medicine, about 1 in 20,000 people have the condition. If the frequency is at all similar in cattle, Americans eat a fair number of XX male cattle without knowing it.
Van Eenennaam pointed out that such a condition would generally go unnoticed in the cattle industry since most male-appearing cattle are castrated and slaughtered. Even if an XX male was allowed to mature into a bull, “he” would fail a breeding soundness exam due to infertility and be culled with no one the wiser.
“It’s likely we’ve eaten them already, but we’ll never know,” Van Eenennaam said of naturally-occurring XX male cattle.
“They’re just boys.” — Kerry Halladay, WLJ editor
