disorders of Sexual development

Question 1

at what week in the embryo are the external genitalia of both sexes identical and have the capacity to differentiate in either direction

Answer 1

week 8

Question 2

what does DHT do

Answer 2

stimulates growth of genital tubercle and induces fusion of urethral folds and labioscrotal swelling

-inhibits growth of vesicovaginal septum preventing development of vagina

Question 3

male external genitalia is entirely formed at the end of ___ weeks

Answer 3

12

Question 4

SRY gene description

Answer 4

one exon, GC rich in 5’ region

-2 zinc finger rich recognition sites for Sp1

Question 5

what does the HMG motif do

Answer 5

• 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

Question 6

HMG octamer mutation means what

Answer 6

no binding to DNA, no male differentiation, 46, XY female

Question 7

SRY translocation to the X chromosome

Answer 7

causes 46, XX to become male

Question 8

____ is required for SRY expression

and development of what requires this

Answer 8

SF1

-gonads and adrenal development

Question 9

what is SF1 required for

Answer 9

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

Question 10

SRY expression in sertoli cells up-regulates what expression

Answer 10

SOX9 expression

Question 11

what does a mutation in the SOX9 gene cause

Answer 11

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

Question 12

how does AMH work

Answer 12

secreted from sertoli cells induced by SOX9

• binds mullerian duct receptors
• serine-thr protein kinases - single transmembrane domain
• apoptosis

Question 13

what is the signifigance of PAR

Answer 13

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

Question 14

DAX1 Gene

Answer 14

normally down-regulated in developing testes but not in ovary

Question 15

mutation or deletion of DAX1 gene =

Answer 15

congenital adrenal hypoplasia and hypogonadotropic hypogonadism
-testicular development occurs
-

Question 16

if you have a duplication of DAX1 in males =

if you have duplication of DAX1 in females =

Answer 16

males = 46, XY female
female = no affect

Question 17

what inhibits DAX1 in males

Answer 17

SRY

-in duplicated state, may be insufficient SRY to repress DAX1 expression

Question 18

intersex

Answer 18

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

Question 19

when an infant has both hypospadias and undescended testis possibility of ___ should be considered

Answer 19

intersex

Question 20

what is hypospadias

Answer 20

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

Question 21

what is DSS

Answer 21

contains DAX1 gene

-regulated by SF1

Question 22

what are 2 different results of SOX9 mutation

Answer 22

XY female sex reversal (46, XY complete gonadal dysgenesis)

-camptomelic dysplasia

Question 23

ovotesticular disorder of sexual development

Answer 23

both ovarian and testicular tissue in one or both gonads

• often ambiguous external genit
• cryptorchidism common
• hypospadias common

Question 24

cholesterol synthesis defects: smith-lemli-opitz syndrome

Answer 24

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

Question 25

male 46,XY DSD male pseudohermaphroditism

Answer 25

due to type 3 isozyme of 17B HSD not functioning

-most freq cause of male pseudohermaphroditism due to testosterone deficiency