Disorders of sexual development Flashcards
define: chimera
- mixture of genetically different cells which originate from different zygotes
- 2 embryos develop as single individual
- double fertilization of oocyte
types of chimeras
- XX/XY –> easily detectable
- XX/XX or XY/XY –> usually no abnormal sexual differentiation
define: mosaic
- 2 or more cell lines from a single zygote
- from a lost or added chromosome (disorder of non-disjunction in mitosis)
- most likely in sex chromosomes
true hermaphrodite
- has both ovarian and testicular tissue
- any combination of ovaries and testes
2 situations of true hermaphroditism
- timing of expression of SRY is shifted (later) so it overlaps with the expression of the ovarian developing program
- male and female supporting cells are simultaneously present (XX/XY chimeras and XY/XO mosaics)
pseudohermaphrodite
- abnormality of phenotypic sex
- chromosomal and gonadal sex are the same, but the phenotype of the internal and/or external genitalia show some features of the opposite sex
male pseudohermaphrodite
XY chromosomes and testes but female characteristics of internal or external genitalia
female pseudohermaphrodite
XX chromosomes and ovaries but masculinized genitalia –> rare
sex-reversal
- both gonadal and phenotypic sex agree but are at odds with chromosomal sex
- true hermaphrodites may occur
XX sex-reversed males
- have testes and are phenotypically male though sterile (XX germ cells can’t survive in testes)
- due to translocation of SRY to X or an autosome
XY sex-reversed females
- female phenotype and ovaries but chromosomally XY
- ovaries degenerate to streak gonads
- due to deletion of Sry
what are androgen based disorders
genetic defects that decrease androgen action in genetic males or increase it in genetic females
what type of gene is androgen receptor the product of
x-linked gene
what does complete deficiency (no AR) lead to
testicular feminization/complete androgen insensitivity (CAIS) –> XY, have testicles (inguinally) but phenotypically taller than average females
hormones involved with CAIS and effects
- not T-AR –> wolffian duct regression (have T, but it can’t work)
- -no DHT-AR –> female external genitalia (have DHT, but it can’t work)
- normal MIS –> mullerian duct regression (have MIS and receptor, so it works)
partial androgen insensitivity syndrome
partial inactivation –> variable phenotype)
5alpha-reductase defects
- have T but can’t make DHT
- normal androgen receptor –> T can function normally
- XY, bilateral testes, normal wolffian structures that en in blind vagina, external female genitalia, female brain sex
what is persistent mullerian duct syndrome in males (PMDS)
- results in male pseudohermaphroditism
- relatively normal males that may have cryptorchidism but also a uterus and oviducts
- from either MIS deficiency or end-organ unresponsiveness
- only homozygous males affected
cryptorchidism in patients with PMDS
- testis tightly linked to retained oviducts
- testes descend, dragging the oviducts and portion of the uterus along into inguinal canal
what deos exposure of female fetuses to MIS during early embryogenesis cause
regression or agenesis of Mullerian structures and later potentially “endocrine sex reversal” of the ovaries (because MIS inhibits aromatase)
what happens to immature ovaries exposed to MIS
reduced aromatase activity and hence produce more testosterone (builds up because they can’t convert it to estrogen)
cause of turner syndrome
usually paternal (the result of defective sperm –> errors in meiosis or mitosis)
cause of kleinfelter’s syndrome
defects arise equally from mother and father due to errors in meiosis
freemartinism info
- requires vascular anastomosis of chorioallantoic vessels between twin cattle placentas
- indifferent gonad of male develops first, produce MIS
- female gonads inhibited by MIS –> mullerian regression
freemartinism and female twin
rudimentary ovary, small vulva, short vagina –> sex-reversed gonads produce testosterone due to inhibition of aromatase enzyme
freemartinism and male twin
reduced fertility and libido
polled/intersex syndrome info in goats
- european dairy breeds
- sex reversed females (XX with testes)
- look female at birth, become more masculine after puberty
- Sry negative but have deletion from chromosome 1 (PIS -/-) –> recessive
how does polled intersex syndrome work
- normal XX females: PIS is normal promoter region that upregulates PISRT1 –> inhibits SOX9 (testis formation)
- PISRT1 is anti-gestis gene
- affected animal: deletions mean SOX9 not inhibited –> testicle forms
- homozygous males are sterile
sex-reversed horses
- XX: sry negatve (downstream issue)
- XY: sry negatve (lack of sry was problem)
hypospadias in dogs
- partial failure of fusion of the urogenital folds
- urethra does not open at the end of the glans penis but further back
- form of male pseudohermaphroditism
- due to inadequate T, inadequate activity of 5alpha-reductase, or defects in downstream genes
XX sex reversal in dogs
- chromosomally female but have bilateral testes, male tracts –> male externally
- XX hermaphrodites
- cocker spaniels
persistent mullerian duct syndrome in dogs
- form of male pseudohermaphroditism
- XY with bilateral testes but half are cryptorchids
- full mullerian strutures
- miniature schnauzers
- autosomal recessive trait
tortoiseshell cats
- black and tabby are autosomal, orange is on X (O is dominant)
- males with O are always orange, females can have one O and one black –> X inactivation –> torties
