Disorders of Sex Development Are an Emerging Problem in French Bulldogs: A Description of Six New Cases and a Review of the Literature.

Disorders of sex development (DSD) are a well-known cause of sterility and reduced fertility in dogs. Here, we report on 6 new cases of DSD in French bulldogs diagnosed by us within the last year. The animals were phenotypical females who underwent detailed diagnosis due to the presence of an enlarged clitoris or a penis-like structure with atypically located urethral orifice (hypospadias). A female karyotype (78,XX) and lack of Y-linked genes (SRY and ZFY) were observed in 5 cases, which were classified as XX (SRY-negative) DSD. Gonads histology could be performed in 4 XX DSD cases: testicular tissue was observed in 3 cases and ovotesticular tissue in 1 case. In the last case, leukocyte chimerism (XX/XY) was detected alongside an ovotestis with epididymis and fallopian tubes. This case was classified as freemartinism. Our study and a literature review showed that heritable XX (SRY-negative) DSD is quite common in French bulldogs, but spontaneously developed freemartinism can be also diagnosed. In conclusion, we postulate that the description of the sexual phenotype of DSD females (enlarged clitoris and presence of testicular tissue) does not distinguish between hereditary XX DSD and nonhereditary freemartinism. Cytogenetic and molecular analyses are thus necessary to correctly diagnose such cases. This is especially important for the French bulldog breed, as a rapid increase in its population could spread hereditary DSD.