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OH NO!!! Just one?!

 

Depending on your breed, that may be a familiar cry of woe. Cryptorchidism is one of those quiet defects lingering just under the surface of many breeds. Certainly there are other more devastating defects that interfere with a dog enjoying life even as a pet such as hip dysplasia or epilepsy. Still, the lack of two descended testicles can destroy your hopes for a stunning male dog in the breed ring or for use at stud.

So how does this happen? It helps to understand the development of a normal male first. The kidneys and the testicles develop very closely together in the canine embryo. In fact, an intermediate stage of kidney development, the mesonephron regresses to become the testicle. Both the kidneys and the testicles are technically outside of the abdominal cavity as they are behind a mesentery that puts them “retroperitoneal” or behind the peritoneum which lines the abdomen. That fact becomes important later during descent into the scrotum.

Since the testicles develop way up by the kidneys, that means they have a long way to travel to reach the scrotal sac. The right kidney is slightly more cranial or towards the head in location which means the right testicle is also slightly more cranial.  In fact, it is felt that the right testicle is more often the one retained, or left inside the body, due to the longer journey it has. Once descended into the scrotum, the left testicle tends to be located slightly higher and behind the right one.

The testicles are pulled down into the scrotal sac by  connective tissue type ligaments called the gubernaculums. This cord regresses towards the scrotal sac, pulling the testicle along with it. Each testicle travels independently on its own side. Eventually the gubernaculums will exist only as a scar that fixes the testicle into its side of the scrotal sac. This action seems to be under the influence of testosterone – but simply giving testosterone injections will not help a wayward testicle.

The scrotal sac itself is continuous with the abdominal cavity so when the testicles enter the scrotum through the inguinal canal (an opening in the muscles that allows the testicles to leave the main body cavity and enter the scrotum) they push the abdominal membranes with them. This can lead to inguinal hernias in dogs whose inguinal canals do not close by 6 months of age or whose canals are quite large to begin with. In these cases, intestines slip into the opening along with the testicles or in place of them.

{jb_left45}Terminology
Cryptorchid – a dog who does not have two testicles in the scrotum
Unilateral cryptorchid – the more common condition in which a dog only has one testicle in the scrotum with the other anywhere from along the penis to inside the abdomen
Bilateral cryptorchid – a dog with no testicles descended into the scrotum – less common than a unilateral cryptorchid
Monorchid – a dog who truly only has one testicle formed – which may be located in the scrotum or in the abdomen – not very common
Anorchidism – a rare condition where there are no testicles developed – externally or internally{/jb_left45}

Normally the testicles have both descended into the scrotum by six to ten days after whelping. They are quite small then and not easy to palpate. Since the inguinal canal is still open and the testicles quite small, they may be pulled back up into the body by the cremaster muscle. Generally both testicles should be palpable and well seated in the scrotum by six to eight weeks of age. Some people will allow up to six months for descent of the testicles but delayed descent such as those cases is possibly a degree of cryptorchidism and associated genetically. Genetic studies in mice have shown a correlation between late descent and eventual cryptorchidism. By six months, the inguinal canal has generally closed down enough to prevent a testicle from moving down or up.

A cryptorchid testicle gets waylaid some where on this journey. It may make it almost to the scrotal sac and end up trapped on the wrong side of the inguinal canal or it may still be way up by the kidney. Surgical removal is always recommended as these testicles are prone to developing cancers and may also twist or torse.

Looking at historical lists of breeds predisposed to cryptorchidism, certain breeds appear on virtually every list. These include: Toy and Miniature Poodles, Pomeranians, Yorkshire Terriers, Dachshunds, Miniature Schnauzers, Maltese, Chihuahuas, Pekingese, Cairn Terriers and Shetland Sheepdogs. Among larger breeds, English Bulldogs, Boxers and Old English Sheepdogs appear. However, virtually every breed and mixed breeds have experienced at least some cryptorchidism. Current studies include Siberian Huskies, Belgian Sheepdogs and Border Collies.  A very informal survey (done with breeders on three small email lists) by me came up with 380 male puppies with 42 cryptorchids, including eight bilateral cyrptorchids. The latest descent was 11 ½ months of age. Eleven breeds and five groups were included. It should also be noted that within a breed, there may be lines that are more or less prone to having cryptorchids. In general, incidence may range from 1.2 percent to 10 percent.

Dr Max Rothschild PhD, Distinguished Professor  of Iowa State University is working on the genetic aspects of cryptorchidism through a grant from the AKC´s Canine Health Foundation. His work is centered around Siberian Huskies with a 14 percent rate of cryptorchidism on their latest health survey. So even breeds not on the standard list can have a fair amount of cryptorchidism present in the breed population.

Dr. Vicki Meyers-Wallen VMD, PhD, Dipl. ACT is a researcher at Cornell University´s Baker Institute for Animal Health. As she points out, “The risk can become higher or lower in a breed over time, depending on the selection that breeders have exercised  (or failed to exercise) to limit or eliminate this trait.” She takes the tough stand that if both testicles aren´t where they should be – firmly in the scrotal sac – by six weeks of age, then the dog should not be considered normal.

Cryptorchidism seems to be influenced by at least three genes but works out in many pedigrees as a simple autosomal recessive that is sex limited. That means both males and females can be carriers, so stud dog and brood bitch both contribute, but in this case, only males show the defect. However, Dr. Rothschild states, “This seems to be a complex trait controlled by multiple genes and is caused not only by genetic components but also by epigenetic and environmental factors.”

Geneticists recommend a minimum of  40 puppies produced as evidence that a dog or bitch does not carry the gene(s) for cyrptorchidism. (And certainly the choice of stud or dam with their own genetic makeup would affect whether any cryptorchid puppies show up.) Most bitches will not produce that many puppies over their lifetimes so their status remains more or less unknown. A male who is a carrier will appear normal (two testicles present in the scrotum) but will pass the defect on to half his offspring. A male who is homozygous for the trait will be a unilateral or bilateral cryptorchid. It is not known how modifier genes affect the unilateral versus bilateral status or the timing of descent. Certainly cryptorchidism is not the simple inherited trait we once thought it was. Still, if a cryptorchid puppy shows up in a litter, it can be assumed that the stud dog is a carrier of this trait and the dam is at least a carrier if not homozygous for the trait. So far no fertility problems have been identified in carrier or homozygous bitches or obvious defects to help identify them before breeding.  

So how do researchers go about tackling this problem? Dr. Rothschild is looking at candidate genes from other species. This means looking at a species where
genes that are associated with cryptorchidism have been identified and then checking out those same areas on the canine genome. When reading genetic research, you will see SNPS mentioned. These are single nucleotide polymorphisms. To go back to your high school biology, a SNP might have the nucleotide C for cytosine in a certain location on one dog´s gene. Another dog might have a T for thymine in that same location. If that is a gene suspected of influencing cryptorchidism, that SNP, or change in nucleotide,  might be significant.

In Dr. Rothschild´s research, he can compare the genome of a “normal” male Siberian Husky to the genome of a cryptorchid dog to see where there are changes in the genetic code. He is currently looking at 75 pairs of Siberian Husky genes to search for a key to this trait.

Dr. Meyers-Wallen has followed a similar path. She started out by checking genes associated with human cryptorchidism in the hopes that there might be a similar causal relationship in dogs. “We did not find mutations in those genes in affected dogs, but the mutations that cause cryptorchidism in humans have not been identified in the majority (over 90%) of the human patients either. Clearly we need to identify canine mutations by other means, rather than waiting for discoveries in human medicine to help us with the dog.”

Using two breeds, Border Collies and Belgian Sheepdogs, Dr. Meyers-Wallen, in collaboration with Dr. Hannes Lohi, has identified a chromosomal region of interest that is likely to contain sequence differences in the gene that should be associated with cryptorchidism. They are looking further to try and identify the exact mutation in that region. Between them, these two research projects have made considerable progress in determining what genes are not involved in canine cryptorchidism. That makes the hunt for the right gene easier.

So while we wait for a genetic test to identify carriers in the case of stud dogs and carriers or homozygous individuals in the case of bitches, what are we to do? For many breeds, if the standard livestock recommendation of not breeding any siblings or the parents of affected dogs again was carried out, we would lose a huge part of our genetic diversity and probably end up with more serious health problems. At least cryptorchid dogs can be neutered and placed as wonderful pets.

Still, it makes sense to never breed a cryptorchid dog as we know he is affected. And yes, cryptorchids are fertile as the one testicle outside the body can produce viable sperm. Certainly we can look at pedigrees and work out the likelihood of producing a cryptorchid puppy in many cases. For example, say your bitch is from a litter with a cryptorchid brother. You are looking at two prospective stud dogs. One is from a litter with two cryptorchid brothers. The other is from a litter with seven males, all intact. It is still no guarantee, but your best bet is the male with no known cryptorchid siblings.

Once a genetic test is available, it will be a major help in planning breeding and knowing early on if a puppy would be a good candidate as a show or breeding dog. It is very likely that many bitches will be affected or carriers as there is currently no way to screen for them. But, if breedings are planned carefully and affected offspring can be identified we can gradually breed away from this fault.

As breeders we can help by supporting research projects such as the two mentioned here. Both money and samples from related and affected dogs can be important for a research project. And who knows, one of your dogs could provide the answer to this genetic defect!

For Dogs in Review
Deb M. Eldredge, DVM