Disorders of Sexual Development

The basic definition of sex used here is biological sex. 'Gender' has many meanings depending on the group or persuasian. It literally means 'kind' or belonging to a group. Thus it is synonomous with biological sex (reproductive anatomy), the behavioral, cultural, or psychological traits typically associated with one sex, or sexual identity, especially in relation to society or culture (see dictionary.com for a long list of explanations).

Historical perspective

Persons with unusual genitalia were called hermapthrodites. In Greek mythology, Hermes is the son of Zeus and the nymph Maia. He is the 'messenger of the gods' and the god of land travel, merchants, weights and measures, oratory, literature, athletics and thieves. Aprhodite is the goddess of love, beauty and sexual rapture. Aprhos means 'sea foam'. She was born when Uranus was castrated by his son Cronus, who threw the genitals into the ocean, which began to churn and foam around them. Aprodite loved many gods. Her son with Hermes was Hermaphroditus, a handsome lad who caught the eye of the nymph Salmacis. Although her overtures to Hermaphroditus were rejected, she wraped herself around him and forcable kissed him. She prays to the gods that they should never part and her wish is granted - and their bodies blend into an intersexual form. He has the body of a woman and the genitals of a man.

Modern perspective

There are many names given to animals with ambiguous or incomplete development of the genitalia. They include sexual ambiguity, intersex, hermaphroditism, sex reversal, feminizing or masculinising conditions and various combinations. It is difficult to categorize all conditions with a single definition, so I will use the term ‘'disorders of sexual development (DSD)'’ and adopt the scheme described by Hughes (2008).

Complete characterisation of an anomaly of sexual development requires the description of the presence of sex chromosomes or genotype, the type of gonad, and the phenotype. As greater sophistication develops, there will be greater complexity in definition with identification of individual genetic, transcriptional or translational abnormalities. In domestic animals, we are often limited to observations of the gonads and phenotype.

Normal male mammals are XY and females are XX. For XY individuals, the gonads should be testes and for XX individuals, the gonads should be ovaries. Just about every combination is possible - there are XX males and XY females.

Introduction

According to the consensis paper by Hughes (2008), the DSD are divided into three major groups: those with chromosomal abnormalities (the Chromosomal DSD), those involving individuals with an XX genotype (XX DSD), and those with an XY genotype (XY DSD).

Chromosomal DSD

Chromosomal DSD include X_ (Turner syndrome), XXY (Kleinfelter syndrome), and various combinations where chimeras and mosaics can be XX/XY and any combinations of reduced or excessive numbers of chromosomes. There are basically 2 different types of chromosomal DSD. Those individuals with aneuploidy, and those with chimerism and mosiacism.

Chromosomal DSD with Aneuploidy

Aneuploidy is an abnormal number of chromosomes, literally an-(not) ploidy (well, good). The normal number of chromosomes is haploid. Diploid is 2 equal sets of chromosomes.

The main types are X_ (monosomy X, Turner syndrome), XXX (trisomy X) and XXY (Kleinfelter syndrome). They occur because of failure of the chromosomes to come apart (nondisjunction) during meiosis (mitotic nondisjunction).

X_ individuals are female with that are infertile. They have afollicular ovaries and the female genitalia can be normal or hypoplastic.

XXX individuals are female, infertile and have underdeveloped genitalia.

XXY individuals are either male or female. Those with ovarian development are females with afollicular ovaries and abnormal female genitalia. XXY males have hypoplastic testes some have a uterus.

Chimeras and Mosaics

A chimera is a mythological creature with the head of a lion, the body of a goat and the tail of a serpent. The mythical centaur, the veterinary symbol, is a chimera. The product of mating of a donkey and horse (mule or hinny) is a chimera. The usual chimera in DSD are XX/XY chimeras which form when the cells of different zygotes fuse. A freemartin is a chimera.

Mosaics are similar but the error is the result of non-disjunction in a single zygote. Examples include XX/X_, XX/XY, XX/XXY. The phenotype is dependent on the amount of testicular tissue. Some have testes, others ovaries and some ovotestes.

XX Disorders of Sexual Development

Mammals with an XX DSD have a genotype that is XX (female) but their chromosomal and gonadal type or phenotype do not agree. This was called XX sex reversal. The subgroupings of XX DSD are based on gonadal type (the type of gonad is either dygenetic, ovotestis or testis), and for those with normal ovaries, there are those with androgen excess from abnormal hormonal or receptor function, and miscellaneous conditions like vaginal atresia and uterine anomalies.

Where possible, the genetic alterations should be included in the complete definition, thus there are XX SRY+ and XX SRY- DSD.

XX DSD, abnormal gonads

These individuals have an XX genotype and gonads that are either dysgenesis, ovotestes or testes.

XX gonadal dysgenesis DSD have primitive gonads, no germ cells, and a female phenotype.

XX ovotesticular DSD have ovotestes and the phenotype depends on the amount of functional testicular tissue present.

XX testicular DSD have testes and a male phenotype.

 

XX DSD, normal gonads (ovaries)

These individuals have an XX genotype, no SRY and ovaries, but have an altered phenotype. External or altered androgen and or receptor function results in virilization of the female. Also included in this grouping are the many different anomalies of the internal or external female tubular genitalia.

 

XY Disorders of Sexual Development

In keeping with the subgrouping of the XX DSD, there are groupings of the XY DSD. Where possible, the SRY status should be included in the definition.

 

XY DSD with abnormal gonads

There are 3 groups of XY DSD. They include

XY gonadal dysgenesis

XY ovotesticular DSD

XY testicular regression DSD

 

XY DSD with normal testes

These individuals have a normal XY genotype, testes but abnormal hormonal or receptor functions. They may also have other anomalies such as cryptorchidism, hypospadias, or persistent Mullerian duct syndrome.

References

Hughes IA (2008) Disorders of sex development: a new definition and classification. Best Practice & Research Clinical Endocrinology & Metabolism 22 (1): 119-134.

 

Poth T, Breuer W, Walter B, Hecht W, Hermanns W (2010). Disorders of sex development in the dog - adoption of a new nomenclature and reclassification of reported cases. Anim Reprod Sc 2010 121: 197-207