Disorders of sexual development in dogs and cats.

Determination of a mammal's sex begins at conception with the establishment of genotype and continues from there as the expression of specific genes directs the bipotential gonad to develop. The gonad further directs the sexual differentiation of the individual. Deviations from either of these pathways at any stage results in disorders of sexual development. Definitive diagnosis minimally requires a karyotype, histopathologic evaluation of the gonads, and gross description of the genital anatomy, with more complete diagnostic answers achieved through other diagnostic tests. This article covers normal and abnormal development of the reproductive organs with emphasis on diagnosis and treatment.

Disorders of sex development in the dog-Adoption of a new nomenclature and reclassification of reported cases.

Intersexuality is a rare congenital abnormality in domestic animals. It is reported in numerous species including the swine, goat, horse, cat, and dog. The present work provides an overview of the variety of intersexual conditions known in different dog breeds. Each case was reclassified based on the described gonadal constitution, reproductive tract abnormalities and karyogram, and categorised according to the stages normal sex development is undergoing resulting in three main categories: (1) sex chromosome disorders, (2) disorders of gonadal sex development, and (3) disorders of phenotypic sex development. Reclassification disclosed that the current classification scheme and terminology are inconsistently used in literature masking the real occurrence and frequency of various intersex conditions in dogs. For establishment of an individual, precise and definite diagnosis, introduction of a new nomenclature is proposed as recently recommended for humans. The new terminology is based on the gonosomal constellation and gonadal constitution, contributes to a systematic classification of canine intersex cases, and replaces the common but confusing diagnoses "true hermaphrodite" and "pseudohermaphrodite". The literature survey was supplemented by adding the results from own investigations in a German Pinscher and Berger Picard dog with bilateral ovotestes and ambiguous external genitalia. The diagnostic approach and clinical, pathomorphological and cytogenetic findings were described in detail.

The case of an Sry-negative XX male Pug with an inguinal gonad.

A case of intersexuality in a Pug that was bought as a male in a pet shop is described. The dog was presented at the Veterinary Teaching Hospital, University of Turin, for a reddish mass protruding from the prepuce. The mass had the aspect of an enlarged clitoris, with a caudoventral direction and a dorsal urethral ostium. A gonad was palpable in the left inguinal region. Laparotomy confirmed ultrasound detection of an abdominal uterine structure together with the right gonad. The histology of both gonads was similar, showing an exclusively masculine character, with seminiferous tubules lined only by Sertoli cells; the uterus showed a normal histological structure. Karyological analysis revealed a female karyotype (78,XX), and polymerase chain reaction showed the absence of Sry. The diagnosis was an XX male. The pathogenesis of the XX sex reversal syndrome in dogs is not completely understood, as Sry, the master gene regulating testis differentiation, is not present; to date, no genetic cause has been identified for this phenotypic condition in dogs. This case is unusual because the dog showed an inguinal testis, implying a partial activity of the mechanisms leading to abdominal testis translocation along a gubernaculum and transinguinal migration.

Sex chromosome abnormalities and sterility in river buffalo.

Thirteen male river buffaloes, 119 females with reproductive problems (which had reached reproductive age but had failed to become pregnant in the presence of bulls) and two male co-twins underwent both clinical and cytogenetic investigation. Clinical analyses performed by veterinary practitioners revealed normal body conformation and external genitalia for most females. However, some subjects showed some slight male traits such as large base horn circumference, prominent withers and tight pelvis. Rectal palpation revealed damage to internal sex adducts varying between atrophy of Mullerian ducts to complete lack of internal sex adducts (with closed vagina). All bulls had normal karyotypes at high resolution banding, while 25 animals (23 females and 2 male co-twins) (20.7%) with reproductive problems were found to carry the following sex chromosome abnormalities: X monosomy (2 females); X trisomy (1 female); sex reversal syndrome (2 females); and free-martinism (18 females and 2 males). All female carriers were sterile.

Sex chromosome chimerism and the freemartin syndrome in Rideau Arcott sheep.

In cattle, nearly all heifers born co-twin to a male are freemartins, XX/XY chimeras that exhibit a characteristic masculinized phenotype. However, in sheep, while litters containing males and females are common, freemartins are relatively rare. The primary aim of this study was to determine the frequency and features of XX/XY chimerism in female Rideau Arcott sheep. Also, breeding records were used to investigate the effect of litter size and sex ratios, as well as the genetic basis of the condition. Finally, the migration and transcriptional competence of cells of the opposite sex in the XX/XY female and male chimeras was explored. Genomic DNA (gDNA) from peripheral blood cells of ewes was screened by PCR for the male-specific SRY gene. Of 230 lambs screened, 10 were identified as chimeras. Litter size and sex ratio showed no statistically significant effect on the frequency of chimerism. PCR and FISH analysis confirmed the presence of opposite sex cells in female and male chimeras, and in the case of ewes, their migration to tissues other than blood. Transcriptional activity of SRY and AMH was detected in gonads of ewes, whereas XIST expression was detected in white blood cells of chimeric rams. It was concluded that the frequency of sex chromosome chimerism in Rideau Arcott sheep is estimated at 4.35%, with no significant effect of litter size and sex ratio. Moreover, as it was shown that opposite sex cells can migrate to tissues other than blood and be transcriptionally active in chimeric sheep, we speculate on the role they can play in these animals.

Independent origin and restricted distribution of RPGR deletions causing XLPRA.

Canine X-linked progressive retinal atrophy (XLPRA) is an inherited blinding disorder caused by mutations in the ORF15 of the RPGR gene and homolog to human retinitis pigmentosa 3 (RP3). The disease is observed in 2 variations, XLPRA1 in Siberian husky and samoyed and XLPRA2 derived from mongrel dogs. A third, neutral, deletion has been described in red wolves. Haplotype analysis of the 633-kbp RP3 interval in 6 different canidae confirmed the same decent for the XLPRA1 mutation in both affected breeds but suggests a recent and independent origin for both forms of XLPRA. The RP3 interval was excluded from causative associations with blindness in the red wolf and akita, a breed closely related to Nordic sled dogs. Overall, these data suggest a limited distribution of the affected haplotypes and indicate that mutations in the ORF15 are likely to be limited to the described dog breeds.

Disorders of sexual development in the dog and cat.

Normal sexual differentiation occurs in three sequential steps--establishment of chromosomal (genetic) sex, development of gonadal sex, and development of phenotypic sex. Errors in the establishment of chromosomal, gonadal, or phenotypic sex cause abnormal sexual differentiation. Affected individuals are identified with a wide variety of patterns from ambiguous genitalia, to apparently normal genitalia with sterility or infertility. When a patient is suspected of having a disorder of sexual development, analysis of the chromosomal constitution and complete gross and histopathologic description of the gonads, internal and external genitalia are required to correctly categorize the type of disorder.