Equine Infertility Answers Could Help Humans


When it comes to mating horses, there’s a lot at stake. Stud fees can soar into the tens and even hundreds of thousands of dollars. And likewise, offspring from a particularly promising pairing can be extremely valuable. These animals could be the start of a new line, and lead to generations of prime performers.

But what happens when normal looking horses with what should be a healthy sex drive display no interest in the other sex…or in mating whatsoever?

University of Guelph biomedical sciences researcher Allan King says they may be inadvertently hiding something – like their gonads.

And that’s if they even have them.

King and his team (Profs. Daniel Villagomez and Tamas Revay, and students Eastman Welsford and Colin Bolzon) have discovered genetic mutations that cause sex reversal in horses. That means genetically male horses develop female reproductive parts on the outside, but male reproductive systems inside.

The King Genetics Lab

“We look at gender as being binary, being ‘either or’, but that’s not always the case,” says King, who at Guelph holds the Canada Research Chair in Animal Reproductive Biotechnology. “Gender covers a spectrum, a whole range from male to female, and these horses fall somewhere in the middle.”

A detailed look reveals that at the start of the reproductive tract, the horses have what you might expect to find in a mare, such as a vulva, clitoris and vagina.

But then things start to change. The deeper you go anatomically, the more the mystery grows: these animals have the internal reproductive organs of a stallion.

Now, these internal organs are not functional. For example, the vagina leads to what’s called a blind-ending uterus. Past that, the reproductive organs are also underdeveloped and non-functional…but rather than being female parts, they’re male.

King and his group are the first ever to discover the reasons behind it in horses. They say it’s caused by a mutated gene called the androgen receptor (AR) gene that influences normal sexual development.

The AR gene makes a protein that attaches to testosterone. It acts like a lock, into which the testosterone key fits or binds. And it influences other genes that regulate normal sexual development before birth and during puberty.

Both males and females have the AR gene. But during embryonic development in a male with a mutated gene, the embryo reverts to producing female reproductive organs. Internally, though, it still has remnants of male testes. Through the horse’s lifetime, these remnants will produce some measure of testosterone.

In the equine sector, these mutations create major issues for horse breeders trying to breed what they think is a mare. In reality, but unbeknownst to the breeders, such horses are sterile. And if they’re paired for breeding, as you can imagine, they don’t like it. Their elevated testosterone levels make them behave like stallions, acting aggressively towards each other.

Such failed breeding sends breeders and their veterinarians on a diagnostic search for the cause of the problem, such as fertility testing. But that kind of testing does not reveal mutated AR genes.

Such problems prompted studies of this behaviour by King’s team dating back to 2011, and have involved three separate horses or horse families.

The first involved an American Quarter Horse named Koko, from near Toronto. When she wouldn’t breed, and her owner brought her to the Ontario Veterinary College to try to determine the problem. Through blood tests, King and his colleagues determined she had elevated testosterone levels. They later discovered a mutated AR gene and discovered she was in fact a genetic male.

They published their findings in a scientific journal called Sexual Development. That prompted a veterinarian from South Africa to contact them about a four-year-old Thoroughbred mare that was found to have abnormally high levels of testosterone after a routine racetrack doping test.

These levels can sometimes indicate the use of performance-enhancing drugs. However, King’s team found she possessed the mutated androgen receptor gene, which prompted the elevated testosterone production.

The third study involved seven offspring of a retired, top-level show jumping Warmblood mare in Denmark — including four sterile sisters, all with the same AR gene mutation inherited from their mother. This mutation was different from the previous cases researchers worked on, but still had the same effect – mares that appeared female on the outside had male reproductive parts internally.

The research team is now examining genetic samples of other animals, including livestock, to determine if similar mutations exist.

King says this research has the potential to help inform the broad spectrum of human sexual development as well. The matter came to light in the 2016 Olympic Games, with South Africa runner Caster Semenya. She won a gold medal in the women’s 800-metre race, but registered abnormally high testosterone levels. An over production of testosterone due to a genetic mutation was found to be the cause.

Funding for this research has been provided by the Canada Research Chairs program and the Natural Sciences and Engineering Research Council.

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