Exam 3: Disorders of Sexual Development

what are the major classes of disorders of sexual differentiation

• gonadal and chromosomal sex abnormalities

• hermaphroditism true and pseudo

• XX/XY chimeras : Freemartinism

describe the gonadal development process shared by males and females

• temporally and in spatial proximity to the developing kidney

• primordial germ cells colonize the gonadal ridge

  • early embryo is bipotential

what happens when the Y sex chromosome is present

• testicular development

• SRY gene encodes for testicular determing factor (TDF), induces formation of Sertoli cells

• Sertoli cells secrete AMH → Mullerian duct regression

• Leydig cells secrete testosterone → Wolffian duct development and external genitalia

what happens when no Y chromosome is present (XX)

• lack of TDF triggers differentiation to female

• persistence of Mullerian duct and regression of Wolffian duct

what caracteristics are used to determine disorders of sexual development

• sex chromosomes

• presence or abscence of genes such as SRY

• gonadal type

• gential phenotype

• any discordance between these leads to sexual ambiguity or intersex

what are the major categories of DSD

• Sex chromosome DSD- abnormal number and or mixture of sex chromosomes
  -XXY Klinefelter
  -X_ Turner
  -XX/XY chimerism

• XX DSD- normal female karyotype, disorder of ovarian development, androgen excess, others

• XY DSD- normal male karyotype, disorder of testicular development, androgen synthesis, others

what generally defines XX/XY chimeras

• two or more types of cells, each with a different chromosomal constitution and each arising from a different source

• hermaprhodite

• different from XX-XY moasics that arise from the same individual by non-disjunction at mitosis in a single zygote

• bovine freemartin

What defines freemartinism

• a genetic female born co-twin with a male

• placental blood vessels between them fuse and exchange blood between fetuses, each fetus becomes a hematopoietic chimera

• male hormones influence a development of female systems

what are the consequences of the male hormones exposed to a freemartin calf

• suppressed development of female organs

• small gonads with no germ cells, induce formation of seminiferous like tubules in ovary

• persistence of male vestiges

what are the gross anatomical consequences of fremartinism

• small ovaries

• small blind uterus (Mullerian duct without communication with vagina

• small vagina with complete hymen

• enlarged clitoris

• seminal vesicles

• male twin is only minimally affected

what defines a true hermaphrodite

• both types of gonadal tissue present testes and ovary

• chromosonal make-up is a chimera: mosaic, XX with or without SRY or uknown

• ducts are abnormal, ambiguous external genitalia

define unilateral hermaphrodite

one side ovotestis

define bilateral hermaphrodite

both sides ovotestis

define lateral hermaphrodite

ovary on one side and testis on other

what is pseudohermaphrotite

• chromosome and gonadal sex agree but genitalia is ambiguous

• one type of gonad by which the individual is classified
  -female = XX ovary
  -male = XY testis

• ducts modified toward other gender

what is the more common incidence of pseudohermaprhodites

males > > > females