Disorders of sex development in the dog: morphologic, genetic and cytogenetic examination in two cases of true hermaphroditism (XXTH)

Investigations of sexual development disorders in dogs and cats are important to identify new mutations, allowing us to eliminate inherited disorders from breeding populations, while contributing to the understanding of mammalian sexual development and differentiation. This work was aimed at giving a deeper insight into peculiar cases of intersexuality, happening in the canine specie, known as XX true hermaphroditism (XXTH), so classified by having both testis and ovarian tissue in one or both gonads in the presence of a XX chromosome constitution. Clinical, histological and genetic approaches were used in the study of a Cocker Spaniel dog 8 months old and a 3 years old mixed breed Pitbull. A normal female karyotype (78,XX) was noticed and polymerase chain reaction (PCR) failed to detect SRY gene on genomic DNA obtained from peripheral blood lymphocytes in both dogs. Female phenotype, hypertrophic clitoris and male behaviour were shown by both dogs. The reproductive tract was removed by standard surgical methods for ovariohysterectomy, and processed for histology. Vaginoplastic was carried out for reconstruction of a normal female phenotype. Histological examination of the genitalia showed bilateral ovariotestis in both cases: the gonad showed immature testicular parenchyma containing seminiferous tubules, Sertoli cells and Leydig cells but no signs of spermatogenesis, together with differently developed ovarian follicles containing oocytes. Genital tracts either of Wolffian and Müllerian origin co-existed in both subjects. Both cases belong to the very rare cases in which testicular tissue develops in the absence of the key gene SRY. Up to date very few genetic events have been associated to this abnormal sexual differentiation: SOX9 over-expression and RSPO1 mutation, nevertheless none of them have been found in dogs.