Introduction

• Abnormalities of sexual developmentand differentiation are complicated and may involve one or more errors of chromosomal sex, gonadal sex or phenotypic sex. Prior to considering the different inter-sex abnormalities, it is vital to understand definition of chromosomal, gonadal and phenotypic sex.
• Normal sexual development requires interplay between the sex chromosomes (chromosomal sex), genes encoding for sexual differentiation (gonadal sex), subsequent hormone production and reproductive tract development (phenotypic sex). Abnormalities may occur anywhere resulting in atypical individuals. Individuals affected by abnormalities of sexual differentiation are therefore best described in terms of their chromosomal, gonadal and phenotypic sex.
• Chromosomal sex:defines or classifies animal by type of sex chromosomes they have. Normal dogs have two sex chromosomes; one from each parent. A chromosomal female has two equivalent sex chromosomes (XX) and a chromosomal male has two differing sex chromosomes (XY). Chromosomal sex may also be referred to as karyotypic or genetic sex.
• Gonadal sex:defines or classifies an animal by type of gonads they develop. Gonadal females have ovarian tissue and gonadal males have testicular tissue. Animals with a mixture of gonadal types, either an ovary and a testis or an ovotestis are referred to as true hermaphrodites.
• Phenotypic sex:refers to the internal and external genitalia being female, male or a combination of both.

Pathogenesis

Etiology

• Abnormalities of Chromosomal Sex:
  • Chromosomal abnormalities may result from abnormal cell division or fusion.
  • Trisomy= presence of three sex chromosomes;monosomy= presence of one sex chromosome. Phenotypic sex of these individuals is generally male (XXY) or female (XXX or XO).
  • Mosaicism= individuals with cell populations of different chromosomal constitution.
  • Chimerism= individual composed of two different cell populations derived from different zygotes. In mosaics and chimeras the type of gonadal sex that develops will vary with the proportion of XX and XY cells. Phenotypic sex will depend upon the subsequent function of the gonads present.
• Abnormalities of Gonadal Sex:
  • Genes responsible for gonadal sex development are still under investigation however, the presence or absence of the sex determining region (Sry) of the Y chromosome and Dax-1 on the X chromosome are known to be important for gonadal sex development.
  • Animals with gonads that do not match their chromosomal sex are referred to as sex-reversed.
  • XX hermaphrodites have both testicular and ovarian tissue.
  • XX males have testicular tissue only.
• Abnormalities of Phenotypic Sex:
  • Development of the phenotypic sex (internal reproductive tract, accessory sex glands and external genitalia) dependant upon presence or absence of testicular tissue.
  • In the absence of testes, internal reproductive tract and external genitalia develop as a female from the mullerian ducts.
  • If testes are present, testosterone and mullerian inhibiting substance (MIS) are released and cause internal reproductive tract and external genitalia to develop as a male from the wolffian ducts. 'Female' mullerian ducts will regress.
  • Pseudohermaphrodites have chromosomal and gonadal sex that agrees, but ambiguous internal or external genitalia.
  • Female pseudohermaphrodites are XX with bilateral ovaries and masculinized androgen responsive organs.
  • Male pseudohermaphrodites are XY with bilateral testes yet have some degree of female internal or external genitalia. They result either from a failure of Mullerian duct regression or failure of androgen-dependent masculinization.

Specific

• Female pseudohermaphroditism may result fromin uteroexposure to exogenous androgens or progestagens during the time of internal and external genitalia development (typically 34-46 days post LH surge).

Pathophysiology

• Infertility.

Diagnosis

Treatment

Prevention

Outcomes