disorders of Sexual development Flashcards
at what week in the embryo are the external genitalia of both sexes identical and have the capacity to differentiate in either direction
week 8
what does DHT do
stimulates growth of genital tubercle and induces fusion of urethral folds and labioscrotal swelling
-inhibits growth of vesicovaginal septum preventing development of vagina
male external genitalia is entirely formed at the end of ___ weeks
12
SRY gene description
one exon, GC rich in 5’ region
-2 zinc finger rich recognition sites for Sp1
what does the HMG motif do
- it is a conserved sequence within the that codes for a protein that induces conformational change in DNA for other factors to bind and direct txn
- binds the minor groove of DNA
- allows the zinc finger proteins to bind SRY region
HMG octamer mutation means what
no binding to DNA, no male differentiation, 46, XY female
SRY translocation to the X chromosome
causes 46, XX to become male
____ is required for SRY expression
and development of what requires this
SF1
-gonads and adrenal development
what is SF1 required for
SF-1 is required for leydig cells to make testosterone
- works on adnrogen receptor, stabilization of wolffian ducts
- DHT on androgen receptor = male different of UG sinus and external genitalia
sexual determination
sexual differentiation
steroidogenesis
lipid metabolism
SRY expression in sertoli cells up-regulates what expression
SOX9 expression
what does a mutation in the SOX9 gene cause
captomelia dysplasia (bent limbs)
- shortened long bones and bowing
- skeletal dysplasia
- 46,XY sex reversal
- no AMH is formed so mullerian ducts do not regress
how does AMH work
secreted from sertoli cells induced by SOX9
- binds mullerian duct receptors
- serine-thr protein kinases - single transmembrane domain
- apoptosis
what is the signifigance of PAR
the psuedoautosomal region is on both the X and Y chrom and inherited in autosomal way
these line up during meoisis 1 and SRY is near this region
-translocation during recombination may take the SRY from the Y and translocate it to the X chromosome
DAX1 Gene
normally down-regulated in developing testes but not in ovary
mutation or deletion of DAX1 gene =
congenital adrenal hypoplasia and hypogonadotropic hypogonadism
-testicular development occurs
-
if you have a duplication of DAX1 in males =
if you have duplication of DAX1 in females =
males = 46, XY female female = no affect
what inhibits DAX1 in males
SRY
-in duplicated state, may be insufficient SRY to repress DAX1 expression
intersex
46, XX/46, XY
- mosaicism
- presence of both genotypes may yield male and female strucutres
- penis underdeveloped
- one or both testes may be palpable but undescended
when an infant has both hypospadias and undescended testis possibility of ___ should be considered
intersex
what is hypospadias
abnormality of anterior urethral development in which the urethral opening is ectopically located on the ventrum of the penis proximal to the tip of glans penis
what is DSS
contains DAX1 gene
-regulated by SF1
what are 2 different results of SOX9 mutation
XY female sex reversal (46, XY complete gonadal dysgenesis)
-camptomelic dysplasia
ovotesticular disorder of sexual development
both ovarian and testicular tissue in one or both gonads
- often ambiguous external genit
- cryptorchidism common
- hypospadias common
cholesterol synthesis defects: smith-lemli-opitz syndrome
deficiency of 7-DHC enzyme, results in abnormal cholesterol metabolism
-prenatal and postnatal growth retardation, microcephaly, mental retardation
-cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly,
syndactyly of toes
male 46,XY DSD male pseudohermaphroditism
due to type 3 isozyme of 17B HSD not functioning
-most freq cause of male pseudohermaphroditism due to testosterone deficiency
