- Definition
- Pathophysiology
- Systems Affected
- Genetics
- Incidence/Prevalence
- Signalment
- Signs
- Causes
- Risk Factors
BASICS
- Sexual differentiation occurs sequentially at 3 levels:
- Genetic/chromosomal
- Gonadal
- Phenotypic
- Errors at any level lead to varying degrees of genital ambiguity and aberrant reproductive function
- Affected animals are known as intersexes or as particular classes of hermaphrodites
- Hermaphrodites/intersex—both testicular and ovarian tissue is present
- Pseudohermaphrodites—further divided into male and female pseudohermaphrodites. Genetic and gonadal sex agree, however there is ambiguous genitalia. Division is dependent on the gonadal tissue present
- Genetic sex is established at fertilization
- Gonadal sex is controlled by genetic sex determination
- Phenotypic sex is governed by gonadal function and target-organ sensitivity
- The zygote contains either an XX (female) or XY (male) complement of sex chromosomes
- The presence of a Y chromosome dictates development of testicular tissue and a male phenotype
- The sex-determining region of the Y chromosome is a gene (Sry) responsible for the initiation of testicular development, regardless of the number of X chromosomes present
- There is no corresponding gene directing female development
- Sex chromosomes
- Abnormal number (aneuploidy)
- Abnormal structure (deletion, duplication/insertion, reciprocal exchange, fusion, inversion)
- Chimeras—individual with coexisting, genetically distinct cell populations admixed in utero. Rare in horses due to separate placentation and uncommon delivery of twins. Fertilization of single ovum by multiple spermatozoa theoretically possible
- Mosaics—individual with coexisting, genetically distinct cell populations caused by errors in chromosomal segregation during division of a single genetic source. Nondisjunction of paired chromosomes during mitosis is implicated: abnormal sexual development occurs when sex chromosomes affected. Sexual differentiation may be ambiguous
- Normality of genetic sex development depends on chromosomal pairings during gametogenesis and fertilization
- 63,XO, monosomy X (most common). Either a normal ovum (X containing) fuses with a sperm lacking sex chromosome or an X-bearing sperm fertilizes ovum lacking X chromosome
- Ovarian dysgenesis, infantile tubular genitalia, small stature, reduced athletic potential, lack of cervical and uterine tone, follicular activity is curtailed, with degeneration occurring during development, phenotypic female; similar to Turner syndrome in humans
- 65,XXY. Either an XY-containing sperm fuses with a normal oocyte or a Y-bearing sperm fuses with an abnormal XX oocyte
- Hypoplastic testes, genitalia normal to hypoplastic, testes may be scrotal or retained, all infertile, phenotypic male; similar to Klinefelter syndrome in humans
- 65,XXX. Either an XX-containing sperm fuses with a normal oocyte or an X-bearing sperm fuses with an abnormal XX oocyte
- Gonadal dysgenesis, infertility, external appearance is most often indistinguishable from a normal mare
- Numerous possible combinations (mixoploidies) are reported, as are deletions of sections (arms) of the sex chromosomes
- Sex reversal syndromes—gonadal and genetic sex may disagree because of autosomal recessive genes or translocation of TDF to X chromosomes. Karyotype is normal
- XY with no testes; instead hypoplastic ovary/streak gonad forms with degenerate follicles/oocytes; acyclic, sterile; female phenotype, therefore classified as XY female
- XX with varying degrees of testicular development, the extreme form is XX male with bilateral testicular development; otherwise, a true hermaphrodite forms with ovotestes
- True hermaphrodite with ovotestes, ambiguous genitalia; named by genetic makeup, either XX or XY
- The presence or absence of an active Sry gene determines the outcome of the reversal
- In the absence of testosterone or anti-Müllerian hormone, a phenotypic female develops
- Phenotypic sex development involves differentiation of tubular genitalia (mesonephric and paramesonephric ducts) and external genitalia under direction of the gonad
- Male reproductive tract—gonad must produce testosterone (Leydig cells) and Müllerian-inhibitory substance (Sertoli cells) at correct time
- Degree of masculinization of external genitalia relates to the proportion of testicular tissue and hence testosterone production of the intersex gonad
- Target organ (duct system) must have cytosolic receptors for testosterone and enzyme 5α-reductase to produce dihydrotestosterone, the androgen responsible for tubular and external genitalia differentiation
- Hypospadias—urethra opens ventrally on penis
- Epispadias—urethra opens dorsally on penis
- Hermaphrodite/intersex—genetic mosaic, both XX and XY present. Alternatively, Sry translocation to X chromosome. The gonad is an ovotestis, with components of both ovaries and testes. External genitalia is ambiguous
- Pseudohermaphrodite—named by the gonadal tissue present; male, testes; female, ovary. Gonadal tissue is either testicular or ovarian, there is no combination. Genetic and gonadal sex are in agreement; ambiguous external genitalia are present
- Testicular feminization—genetic and gonadal male (XY chimera, testicle) but external genitalia female; target-organ insensitivity
- Congenital disorder
- Normal external genitalia may delay detection of the problem until the affected individual enters a breeding program
- Infertility; sterility
- Failure to display appropriate reproductive behavior with opposite sex; attraction to same sex
- In females, apparent estrus behavior but lack of standing for mounting. Ovarian inactivity during breeding season
- In males, normal libido, however ejaculate consistently azoospermic
- Female—normal or hypoplastic vulva; enlarged clitoris; presence of os clitoris; purulent vulvar discharge
- Male—penis, prepuce normal or hypoplastic; testes, scrotal or cryptorchid; hypospadias, epispadias (abnormal position of urinary orifice, closure of urethra)
- Congenital—heritable or spontaneous genetic abnormalities
- Genetic abnormalities—zygote fusion, abnormal sex chromosome number or structure
- Transfer of TDF to autosomal chromosome or X chromosome
- Placental admixture not reported in equines due to separate vascularity (contrast bovine freemartinism)
- Exogenous—steroid hormone use during pregnancy
- Progestins, androgens—masculinize females
- Estrogens, antiandrogens—feminize males
DIAGNOSIS
TREATMENT
FOLLOW-UP
MISCELLANEOUS