Thursday, March 26, 2009

Visit to Baker Institute for Animal Health

The last few days have been really busy for us and puppies, and it is time to catch up. Pups have had two training liver drags/blood lines. They are progressing nicely. Yesterday, however, we focused on a different aspect of dog breeding.

Puppies are 9.5 weeks old, and we noticed that Ollie's testicles have not descended into his scrotum yet. After I had done some reading on the topic, I contacted Dr. Vicki Meyers-Wallen from Baker Institute for Animal Health at Cornell University in Ithaca, NY, and made an appointment to bring in puppies and their parents.

Puppies are in top two crates and Emma and Joeri in the bottom two. Puppies took a three-hour-drive really well, and it was good socializing experience for them.
The James Baker Institute's website explains the condition called cryptorchidism:

Cryptorchidism is the failure of one or both testes to descend into the scrotum. It can occur as the only defect in male development (isolated cryptorchidism) or in association with other disorders of sexual development, such as PMDS or SRY-negative XXSR (above). In the dog, both testes normally descend into the scrotum by 2 weeks after birth (even though one can not easily feel them there at that time), but should certainly be detectable in the scrotum by 6 weeks of age. Since isolated cryptorchidism is the most prevalent inherited disorder of the reproductive system reported in dogs, it would be very helpful to have a DNA test to detect carriers of the causative mutations. The remainder of this text refers only to isolated cryptorchidism.

Based on the few pedigree studies in dogs and experimental studies in other animals, testis descent in the dog could be regulated by at least 3 known genes, as well as others that are presently unknown. Mutations in such genes impair the ability of the testes to descend, resulting in cryptorchidism. Delayed descent of the testes may be a less severe form of cryptorchidism, as it shown in some mouse studies. It has been shown in other animals, such as pigs and goats, that the prevalence of cryptorchidism in herds can be reduced over time by selecting against this trait. That is, cryptorchid animals and male and female parents of cryptorchid animals were not used as breeding stock. This approach has not been used extensively in purebred dogs. However, if both male and female carriers could be identified by a practical test, then one could more easily avoid producing affected offspring.

Bilaterally cryptorchid dogs have no testes in the scrotum and are sterile. Unilaterally cryptorchid dogs have one testis descended, and while of lower fertility, can reproduce. An undescended testis may lie within the inguinal (groin) area or within the abdomen and has an increased risk of developing tumors. Additionally, use of affected dogs as breeding stock can eventually lead to increasing numbers of unilaterally and bilaterally cryptorchid dogs in the line or breed. Therefore neutering of affected dogs (surgical removal of both testes) is recommended. To prevent surgically corrected cryptorchid dogs from being deceptively presented as normal, the American Veterinary Medical Association states that it is unethical for a veterinarian to surgically correct this condition without also neutering the animal. Although medical treatments have been proposed for this condition in the dog, there is no evidence that any are efficacious. It is important to note that neither surgery nor medical treatment will alter the affected dog’s genetic makeup. Thus, reproduction from affected dogs and medical treatment of affected dogs may not be in the long term best interest of the breeder, or the breed. Also, breeding of animals with late descending testes may produce more with this condition, and worse, dogs in which the testes fail to descend at all.

Our laboratory is collaborating with other investigators to identify mutations that cause cryptorchidism in dogs. We have not yet found mutations causing canine cryptorchidism, and need to examine DNA from more affected dogs, their related family members, and dogs of several breeds. All participants in our studies are purebred dogs, but their identity and that of their owners is held in strict confidence. Using DNA markers, linkage analysis and association studies, we are presently working to identify the chromosome location of genes responsible for canine cryptorchidism. Our final goal is to produce practical tests to easily identify male and female carriers of mutations that cause cryptorchidism. This will allow breeders to avoid production of cryptorchid offspring while maintaining the desirable traits in their line and breed.

Testis descent is a complex developmental process likely to involve several genes, including those directly controlling testosterone synthesis, the androgen receptor (AR), insulin-like factor 3 (INSL3) and its receptor (GREAT) and calcitonin gene-related peptide (CGRP). For example, any genes encoding enzymes in the steroidogenic pathway leading to testosterone production or stimulating INSL3 secretion could theoretically be involved. Mutations affecting factors listed above account for only a small percentage of human cryptorchidism, so additional genes are likely to be involved, and none has been identified as causative of canine cryptorchidism.

Dr. Vicki Meyers-Wallen examined Oak and Ollie, and blood was collected from them and their parents, Joeri and Emma, for DNA studies.

Above: Ollie is being examined by Vicki Meyers-Wallen. Below: a blood sample is collected from Ollie for DNA studies.

Puppies will be going to their new homes in the 2nd and 3rd week of April, so we will be able to monitor Ollie's testicles for a while yet. They may come down eventually, but basically he should not be used for breeding, and he will be sold on the limited registration.

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