Intersex

Introduction

Intersex encompasses developmental abnormalities resulting in discordance between genetic, gonadal or phenotypic sex.

The reason for the abnormalities is usually unknown, but a form of inheritance may be involved, sex chromosomes may be abnormal, or the foetus may have been exposed to androgenic or progestational hormones.

Abnormalities of chromosomal sex

Chromosomal defects include:

True hermaphrodite: Chimeras and Mosaics: which possess both ovaries and testicles. This is rare condition but can occur in all species. Failure of embryological differentiation of gonads during foetal life leads to the presence of both ovarian and testicular tissue (ovotestis or one of each type). The tract is predominantly female, although there is often an enlarged clitoris and reduced vulval lips. The animal is usually XX with H-Y antigen (protein normally coded for by Y chromosome).

XXY syndrome: Klinefelter's syndrome: usually in tricolour male cats with male phenotype but degenerate germ cells. It has been reported in cats, bulls, rams and boars. There is normal autosomal chromosome complement. Testes form normally, but all germ cells die when they enter meiosis due to the activity of two X chromosomes as opposed to the normal one.

XO syndrome: Turner's syndrome: there is a small, infantile female reproductive tract and an absence of cycling. The syndrome occurs in mares and has normal autosomal chromosome complement. An ovary develops but there is only one active X chromosome, so oocytes die. The death of oocytes is followed by loss of follicles. This leads to ovarian dysgensis (abnormal development) and a highly regressed streaky ovary that does not secrete the normal ovarian steroid hormones. The ovary therefore lacks tone and has no follicular cycles. Morphologically, there are normal external genitalia, small stature, flaccid uterus, small, inactive ovaries and complete absence of ovarian activity and consequent anoestrous.

XXX syndrome: abnormalities in the oestrous cycle and infertility are often present.

Abnormalities of gonadal sex

This includes the sex reversal syndrome, in which there is a disagreement between the chromosomal and gonadal sex in the affected individual.

XX sex-reversal animals have a normal female karyotype but also some degree of testicular differentiation in their gonads.

XY sex-reversal is when animals have a male karyotype, a female phenotype, but develop gonadal dysgenesis where neither true ovarian nor testicular differentiation occurs. 15% of XY females have SRY mutations or deletions and usually have complete failure of testis development and testicular hormones yet do not develop ovaries.

Abnormalities of phenotypic sex

Abnormalities in the development of the internal and external genitalia can occur in at least three ways:

• if the primordium of the internal or external genitalia fails to develop, then the genitalia fail to develop
• errors in chromosomal or gonadal sex lead to a failure of development of functional gonads and the development of the genitalia is affected.
• disorders in hormone production or reception lead to phenotypic abnormalities.

Pseudohermaphrodism is when the chromosomal and gonadal sex are in agreement but the internal and external genitalia have some features of the opposite sex due to abnormalities in hormone production or reception.

Female pseudohermaphrodites have XX chromosomes and normal ovaries but the internal and external genitalia undergo partial or complete androgen-dependent masculinisation. The androgen source can be exogenous or endogenous. In the dog this is usually seen when steroids are administered during gestation.

Male pseudohermaphrodites have XY chromosomes and normal testes but have defects in Mullerian duct regression or androgen-dependent masculinisation. The uterus, oviducts and cranial vagina may be present and cryptorchidism may occur.

Male pseudohermaphrodites are commonly found amongst pigs and goats. In goats, the characteristic is linked to a gene for polledness (dominant); homozygotes are hermaphrodites with a wide range of masculinisation.

Clinical Signs

General signs in most species include abnormal external genitalia, and:

Phenotypic females: infertility, irregular cyclicity, failure of conception, small litters, complete failure to cycle and abortions, os clitoris and clitoral enlargement.

Phenotypic males: azoospermia, oligozoospermia, high percentage of abnormal nonmotile sperm, testicular hypoplasia, cryptorchidism, low libido, intermittent haematuria and pyometra.

Diagnosis

There may be a history of administration of exogenous androgens or progestins during pregnancy.

The animals may be presented for abnormal external genitalia.

On physical exam: the external genitalia should be examined and a rectal examination should be performed to check for the prostate in dogs.

Gonad histology can be performed to determine the structure and hormonal function.

Karyotyping can be performed.

H-Y: male histocompatibility antigen assay and androgen receptor assays can be performed.

Treatment

There is no curative treatment.

Usually intersex animals can lead normal lives but they will probably be infertile.

They can be neutered to minimise the risk of tumours, pyometra and abnormal behaviour.

A clitoridectomy may be performed in some female dogs if the clitoris is very large.

The prognosis is good for life.

Equine conditions

XY Sex-reversal: this is an inherited trait with XY karyotypes but variably female phenotype of external genitalia. There is a wide range of morphology from near-normal tract with inactive ovaries, to hypoplastic ovaries or ovotestes with aplastic genital tract. The condition is thought to involve Y chromosome mutation.

Testicular feminisation

There is an XY genotype with testosterone production but sterile gonads internally and female external genitalia. The vagina is blind-ending with absence of internal genital tract. These male pseudohermaphrodites exhibit male behaviour and have significant testosterone levels. Testes develop normally and secrete androgens and MIH. Foetal genetalia are genetically insensitive to the actions of androgens due to a point mutation in the androgen receptor. Consequently, Wolffian ducts regress, allowing formation of female external genetalia (labia, clitoris, vagina). Sertoli cells are present and continue to secrete MIH, causing Mullarian Duct regression. Since both Wolffian AND Mullarian ducts regress, there is no internal genetalia.

Intersex Learning Resources
Flashcards Test your knowledge using flashcard type questions	Small Animal Abdominal and Metabolic Disorders Q&A 10

References

Pasquini, C. (1999) Tschauner's Guide to Small Animal Clinics Sudz Publishing

Ostrander, E. (2007) The dog and its genome CSHL Press