Disorders of Sexual Development Flashcards
What are some teratogens associated with hypospadias?
- rubella virus
- oral contraceptives
- ethanol
- anticonvulsants
- cocaine
- vitamin A
What are some teratogens associated with ambiguous genitalia?
- progestational agents
- anticonvulsants
What are some teratogens associated with cryptorchidism (undescended testicle)?
- Rubella virus
- Anticonvulsants
*review embry
ok
What are main 2 types of cells that testis produces?
Leydig + Sertoli cells
How does a bipotential gonad develop into a testis?
presence in SRY gene
What do Leydig cells produce?
testosterone –> helps dev male reprod structures
Who do Sertoli cells produce?
Anti-Mullerian Hormone (AMH)
AKA Mullerian inhibiting substance
leads to regression of Mullerian duct
Sertoli cells (that produce AMH) are able to support spermatogenesis how?
- from spermatogonia to spermatid to spermatozoa
- stim by FSH
- secretes androgen binding hormone (ABP) to help concentrate testosterone in lumen of the seminiferous tubule
Leydig cells (AKA interstitial cells of Leydig) are located where?
adjacent to seminiferous tubules in testis
Leydig cells (AKA interstitial cells of Leydig) are stim by what?
stim by leutinizing hormone (LH) to produce testosterone
contain cholesterol-lipid droplets –> needed for testosterone production
What does the Wolffian system include?
- seminal vesicles
- vas deferens
- ejaculatory duct
- prostate
note, men need testosterone to FORM these
What do the Mullerian ducts include?
- fallopian tubes
- uterus
- vagina
note, men need AMH to make these fade away
What (thinking embry) produces primoridla tissues of external genitalia in both sexes?
proliferation of mesoderm and ectoderm around cloacal membrane
Primorida are indistinguishable up until when?
week 12
so all bipotential until 12w
What is the most common cause of CAH?
CYP21A2 gene
excessive adrogens from the missing enzyme 21-hydroxylase
What would you typically see on US for CAH?
uterus and ovaries
can have variety of external anatomical
in the newborn period, CAH can impact ___ levels?
cortisol (and other hormones)
What is X-linked adrenal hypoplasia congenita caused by?
mutation of NR0B1 gene –> affects DAX1 protein
If you see hypospadias + undescended testicle + adrenal insufficiency –> what do you think?
X-linked adrenal hypoplasia congenita
46,XY
What is Androgen Insensitivity Syndrome cause by?
AKA testicular feminization
mutationsin androgen receptor
- X-linked
What are the external gen of those w Androgen Insensitivity Syndrome?
since they lack virilization bc androgen receptor not functioning and cannot bind testosterone or DHT –> normal female gen w Undescended testes
What are the internal organs of those w Androgen Insensitivity Syndrome?
so they do NOT have uterus or cervix
they DO have external female genitalia + undescended testes
What is the X-linked recessive cause of Kallman syndrome?
KAL1
What are the AD causes of Kallman syndrome?
FGFR1, PROKR2, PROK2, CHD7 or FGF8 genes (causing KS types 2, 3, 4, 5 and 6, respectively)
What are the AR causes of Kallman syndrome?
PROKR2 and PROK2
What are the main features assoc w Kallman syndrome?
(can be X-linked, AD, AR)
- hypogonadotropic hypogonadism
- dec sense of smell
- undescended tests and/or hypospadias
- other anomalies too
What is one organ system you definitely want to check when thinking of DSD?
kidneys
What are the DSD implications with Campomelic dysplasia?
so the SOX9 gene causes sex reversal
external genitalia not look male or female
OR
normal female genitalia w typical male chromosome pattern (46,XY)
What are the DSD implications in SLO?
(caused by def of enzyme 7-dehydrocholesterol reductase) –> chel metab disorder
(DHCR7)
underdeveloped external genitalia in males (so not form testicles or ovaries)
What is WT1 responsible for?
WT1 –> protein imp in renal and gonadal development
WT1-related disorders = Frasier, Denys Drash
What is Frasier syndrome?
WT-1 related disorder
46,XY complete gonadal dysgenesis
- nuc 4-5 of intron 9 in WT1 gene
What is Denys Drash?
WT1-related disorders
XX or XY
- abnormal devel of external gen in males
- 90% have Wilm’s tumor
What would an SRY translocation OR dup of either SOX9 or SOX3 lead to?
46, XX karyotype –> male
so they have XX but also SRY –> leads to male external genitalia from normal –> ambiguous
- small testes, gynecomastia
- azoospermia
- absence of Mullerian structures
identifying male need testosterone supplementation
What is Persistent Mullerian Duct syndrome?
46,XY
Mutation in MIS or AMH (MIS receptor)
this leads to the paramesonephric ducts PERSIST, meaning that there is a small uterus + paired fall tubes
What is 5a-reductase deficiency?
46, XY
mutation in 5a-reductase
- so this is needed for converting testos into its more potent androgen DHT (dihydrotestosteron)
they have mesonephric ducts (since these only need testos) + normal production of MIS from Sertoli cells –> paramesonephric duct regression
Describe mosaic Mixed Gonadal Dysgenesis
chromosomal mosaicism 45,X;46,XY
- genital diff at birth w asym of int + ext anatomy
- gonads - dysgenetic
- wait some time then determine pheno
note, more male phenotype = less cancer risk
note, used to have surgery right away; now wait
What syndrome accounts for 15% patients w primary amenorrhea
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH)
XX
- variable anatomy, most w vag dimple
- normal ovaries + fall tubes
- rudimentary uterine remnants
