Normal sexual development in mammals involves 3 steps: establishment of chromosomal sex, development of gonadal sex, and development of phenotypic sex. Fertilization determines chromosomal sex, but all embryos are sexually indifferent. Presence of a Y chromosome results in differentiation of the genital ridge into a testis, and in the absence of a Y chromosome the genital ridge develops into an ovary. The SRY gene located on the Y chromosome is necessary for activation of testis formation or suppression of genes that encode ovarian formation. Disorders of chromosomal sex result from defects in the number or structure of the sex chromosomes. Recognized syndromes include XXY, XO, XXX, true hermaphrodite syndrome, chimeras, XX/XY chimeras with testes, and XY/XX chimeras with testes. Patients with disorders of gonadal sex have an XX or XY chromosome constitution, but the gonadal sex does not agree with the chromosomal sex-in other words, the animals are "sex reversed." This condition has been identified as an inherited autosomal recessive trait in American cocker spaniels and German shorthaired pointers, and as familial in other breeds. Some of the more common include phenotypic females with anestrus and genital abnormalities and males with bilateral cryptorchidism and an abnormal prepuce and penis. In disorders of phenotypic sex, the chromosomal and gonadal sex agree, but the internal or external genitalia or both do not. Clinical syndromes include female pseudohermaphroditism, male pseudohermaphroditism, persistent Müllerian duct syndrome, and defects in androgen-dependent masculinization. Disorders of sexual development present with a wide range of clinical signs and may not be evident unless the animal is involved in a breeding program. Differentiation requires careful clinical examination and analysis of chromosomes.
COMMENTARY: Small animal practitioners may be confronted with a case that reminds them that there is no such thing as a routine spay. At other times they may be confounded by the infertile pet or one that outwardly appears somewhere between male and female. Due to the infrequent occurrence of such cases and the multitude of underlying causes, most practitioners need guidance in sorting through the disorders of sexual development. More than a basic knowledge of developmental genetics and anatomy is essential to properly classifying these disorders. It is imperative that sound anatomic, histopathologic, and chromosomal analysis be made in cases where accurate diagnostics are needed. Practitioners should endeavor to collect and preserve tissues for diagnosis in abnormal cases. A limited number of laboratories provide karyotype analysis. Utilizing the expertise of a pathologist with a special interest in reproductive disorders is also recommended. -- Kit Kampschmidt, DVM
Disorders of sexual development in the dog and cat. Lyle SK. THERIOGENOLOGY 68:338-343, 2007.