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

Abstract

nosed. 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. © 2020 S. Karger AG, Basel Disorders of sex development (DSD) are a well-known cause of sterility and reduced fertility in domestic mammals, including dogs. They can be classified by sex chromosome constitution into 3 major categories: (a) DSD caused by an abnormal set or structure of sex chromosomes, called sex chromosome DSD; (2) DSD with a normal female set of sex chromosomes, referred to as XX DSD, and (3) DSD with a normal complement of male chromosomes, XY DSD [Poth et al., 2010;Meyers-Wallen, 2012]. Moreover, information about the presence or absence of the SRY gene, which is crucial for male development, can bring additional knowledge about the DSD Keywords CNV · Dog · Freemartinism · Hypospadias · Intersexuality · SOX9 Abstract 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 diag-

A clue to the etiology of disorders of sex development from identity‐by‐descent analysis in dogs with cryptic relatedness

“…No gene was found to explain all XX DSD cases. In accordance with previous results, the present findings suggest, but do not imply, heterogeneity in the etiology of XX DSDs (Szczerbal et al, 2019). That a causative mutation (apart from SOX9 ) has not yet been found in analyses of the various sporadic cases may indicate the presence of a few still unknown mutations.…”

Cellular fate of intersex differentiation

“…Gonadal dysgenesis and ovotestis phenotype are often prevalent in animals, including dogs, cats, birds, fishes, amphibians, and reptiles [25][26][27][28][29] . In some animals, ovotestis formation is a physiological process, not a pathological condition, for example, in the teleost Monopterus albus, a new model species for evolution, genetics and development 26 .…”

Analysis of XX SRY-Negative Sex Reversal Dogs

“…Differently from other XXSR males, described in the literature and cited by [ 29 ], prostate was completely absent, and there was an abnormal vulva with an enlarged clitoris containing a bony base. This condition is the most frequently observed in French Bulldogs [ 30 , 31 ].…”