Canine Persistent Müllerian Duct Syndrome (PMDS)
Canine Persistent Müllerian Duct Syndrome (PMDS) is a form of male pseudohermaphroditism, an inherited disorder of sexual development, affecting the Miniature Schnauzer dog. The disorder is characterized by presence of Mullerian ducts, such as uterus, Fallopian tubes and upper vagina, while the external genitalia appears normal on the affected dogs. PMDS has been reported in Miniature Schnauzers in Northern America, Europe and Asia. This canine disorder shares characteristics with its human equivalent of PMDS, which makes it an important animal model for the disease’s study.
Characteristics and Symptoms
During embryonic development, Mullerian ducts regress shortly after development of testes, which is induced with working of two distinct hormones produced by the fetal testes. Those hormones are testosterone, produced by Leydig cells, and anti-Mullerian hormone (AMH), secreted by Sertoli cells. Testosterone mediates the action necessary for the prostate formation and masculinization of the external genitalia, while AHM is responsible for regression of Mullerian structures. In case of mutation in the AHM gene, failure of regression of Mullerian structures will occur.
PMDS affected Miniature Schnauzers are male dogs with normal karyotype, 78 XY. They have normal male phenotype and complete male internal genitalia, including vasa deferentia, and a prostate, but internally Mullerian and Wolffian duct system is present. All layers of uterus are present, although the lack of ovarian hormonal stimulation. Approximately 50% of affected dogs are either unilaterally or bilaterally cryptorchid, are lacking one or both testes from the scrotum. Histological examination of cryptorchid testes in PMDS dogs reveals absence of germ cells. Affected dogs with bilateral scrotal testes are fertile, but their sperm counts are lower than expected for the body weight. Dogs with bilateral cryptorchidism are sterile, while PMDS males with unilateral cryptorchidism are subfertile and with lower sperm counts than in unaffected dogs with similar body weight.
Older PMDS dogs with cryptorchidism are often affected with Sertoli cell tumor, as well as pyomtra (uterine infection), urinary obstruction and urogenital tract infections.
Persistent Müllerian Duct Syndrome Miniature Schnauzer Type is caused by a mutation of AMHR2 gene, also known as the MISRII gene (Mullerian inhibiting substance type II receptor). The mutation causes expression of truncated protein, which results in failure of regression of Mullerian structures.
The disorder is inherited as autosomal recessive disorder, but affects only male dogs, which makes it sex-limited. Dog can be clear, carrier and affected. Affected can be only male dogs, while carriers can be both male and female dogs. When mating two carrier dogs, there is a 25% chance of obtaining an affected puppy. Since affected dogs may appear as normal externally and still be fertile, genetic testing is higly recommendable in order to eliminate the mutation from the dog breed.
Wu X, Wan S, Pujar S, Haskins ME, Schlafer DH, Lee MM, Meyers-Wallen VN. A single base pair mutation encoding a premature stop codon in the MIS type II receptor is responsible for canine persistent Müllerian duct syndrome. J Androl. 2009 Jan-Feb; 30(1):46-56.
Wu, X., Wan, S. et al (2009.): A Single Base Pair Mutation Encoding a Premature Stop Codon in the MIS type II receptor is Responsible for Canine Persistent Müllerian Duct Syndrome. J Androl. 2009 ; 30(1): 46–56. doi:10.2164/jandrol.108.005736.
Vegter, AR., Kooistra, HS., Sluijs,van FJ (2010): Persistent Mullerian Duct Syndrome in a Miniature Schnauzer Dog with Signs of Feminization and a Sertoli Cell Tumor. Reprod Dom Anim 45, 447–452 (2010); doi: 10.1111/j.1439-0531.2008.01223