SM_199b: Sexual Differentiation: Normal and Abnormal Flashcards
Describe sex development
Sex development
- Chromosomal sex
- Sex differentiation via ovary-determining genes or testis-determining genes
- Gonadal sex
- Sexual differentiation via gonadal steroids
- Phenotypic sex
Chromosomal sex is developed via ____
Chromosomal sex is developed via meiosis
(nondisjunction can occur)
Describe development of gonadal sex
Gonadal sex development
- First few weeks: gonad starts to develop primordial germ cells in yolk sac
- 5-6th week: urogenital ridge develops further and germ cells migrate from hindgut to genital ridge
- Differentiation occurs by 8 weeks of differentiation
- Ovary develops later after week 10 and requires presence of germ cells
____ is necessary for development of gonads and adrenal glands
SF1 is necessary for development of gonads and adrenal glands
____ and ____ must act for testis formation
SRY and SOX9 must act for testis formation
___ must be suppressed and ___ active for ovarian development
SOX9 must be suppressed and WNT4 active for ovarian development
Describe development of reproductive tract
Reproductive development tract
Sertoil cells secrete ____ to promote Mullerian regression
Sertoil cells secrete AMH to promote Mullerian regression
Leydig cells secrete ____ and ____ to promote male sexual differentation
Leydig cells secrete testosterone and DHT to promote male sexual differentation
Describe AMH (anti-mullerian hormone)
AMH (anti-mullerian hormone)
- Produced by Sertoil cells
- Regulated by SF1 and SOX9
- Causes regression of mullerian structures
- Paracrine effects: AMH from testis causes regression on ipsilateral side
- Described human mutations of AMH are in 46 XY individuals with persistent mullerian duct syndrome
5 alpha reductase 2 mediates ____ and is required for ____
5 alpha reductase 2 mediates conversion of testosterone to dihydrotestosterone and is required for masculinization of external genitalia
Describe phenotypic sex development
Phenotypic sex development
Compare and contrast 46 XY and 46 XX development
46 XY and 46 XX development
Sex development and gender development are ____
Sex development and gender development are different
Disorders of sexual development can present at ___
Disorders of sexual development can present at any time
Describe disorders of sexual development
Disorders of sexual development
- Sex chromosome DSD
- 46 XY DSD: disorders of gonadal development, disorders of androgen synthesis or action
- 46 XX DSD: disorders of gonadal development, androgen excess
Described mixed gonadal dysgenesis
Mixed gonadal dysgenesis
- Variable external genitalia
- Variable internal genitalia
- Often asymmetric
- Gender identity: more male but varies
- Pubertility / fertility: may produce testosterone and sperm
- Increased rate of germ cell tumor
Describe overtesticular DSD
Overtesticular DSD
- Variable external genitalia
- Variable internal genitalia
- Gender identity: varies
- Puberty / fertility: can produce testosterone or estrogen, subfertility but can produce sperm or eggs
- Mildly increased rate of germ cell tumor
Compare and contrast mixed gonadal dysgenesis and ovotesticular DSD
Mixed gonadal dysgenesis and ovotesticular DSD
Describe 46 XY DSD
46 XY DSD
- Disorders of gonadal development affect gonadal sex
- Disorders of androgen synthesis or action affect phenotypic sex
Describe complete gonadal dysgenesis
Complete gonadal dysgenesis
- Female-typical external genitalia
- Mullerian structure present
- Gender identity: usually female
- No puberty, no gametes, but can carry pregnancy
- Increased rate of germ cell tumor
Describe partial gonadal dysgenesis
Partial gonadal dysgenesis
- Variable external genitalia
- Variable internal genitalia
- Gender identity varies
- Testosterone and sperm but varies based on testicular function
- Increased rate of germ cell tumor
Compare and contrast complete gonadal dysgenesis, partial gonadal dysgenesis, and ovotesticular DSD
Complete gonadal dysgenesis, partial gonadal dysgenesis, and ovotesticular DSD
Describe complete androgen insensitivity syndrome
Complete androgen insensitivity syndrome
- Female-typical external genitalia
- No mullerian structures
- Gender identity: usually female
- Testosterone converted to estrogen, no gametes
- Mildly increased rate of germ cell tumor
Describe partial androgen insensitivity syndrome due to AR mutation
Partial androgen insensitivity syndrome due to AR mutation
- Variable external genitalia
- Gender identity varies
- Variable testosterone effect, sperm production possible
- Increased rate of germ cell tumor
Describe partial androgen insensitivity syndrome due to 5-alpha reductase deficiency
Partial androgen insensitivity syndrome due to 5-alpha reductase deficiency
- Variable external genitalia
- Gender identity: more often male
- Some testosterone at puberty, sperm production possible
- No increased rate of germ cell tumor
Compare and contrast complete androgen insensitivity, partial androgen insensitivity, and 5-alpha reductase deficiency
Complete androgen insensitivity, partial androgen insensitivity, and 5-alpha reductase deficiency
Describe 46 XX DSD
46 XX DSD
- Disorders of gonadal development affect gonadal sex
- Androgen excess affects phenotypic sex
Compare and contrast testicular DSD and ovotesticular DSD
Testicular DSD (XX + SRY) and ovotesticular DSD
Describe CAH due to 21 hydroxylase deficiency (salt-wasting)
CAH due to 21 hydroxylase deficiency (salt-wasting)
Describe congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- Salt-wasting
- Cortisol deficiency
- Low Na, high K
- Lethargy, poor feeding
- Starts at 5-7 days of life
- Replace with Florinef and Cortef
- Gender idnetity is usually female
- Estrogen and eggs
Infant with penoscrotal hypospadias, scrotal tissue rugated on the right but flat on left, right testis palpable in scrotum but left testis nonpalpable
Ultrasound: small mullerian structure present
Most likely diagnosis is
____
Infant with penoscrotal hypospadias, scrotal tissue rugated on the right but flat on left, right testis palpable in scrotum but left testis nonpalpable
Ultrasound: small mullerian structure present
Most likely diagnosis is mixed gonadal dysgenesis
(asymmetry)
Infant born with prominent clitorophallic structure, single urogenital sinus, fused labioscrotal tissue (no hyperpigmentation or rugation), no palpable gonads
Ultrasound: Mullerian structure present
Karyotype: 46 XX
Most likely diagnosis is ____
Infant born with prominent clitorophallic structure, single urogenital sinus, fused labioscrotal tissue (no hyperpigmentation or rugation), no palpable gonads
Ultrasound: Mullerian structure present
Karyotype: 46 XX
Most likely diagnosis is CAH due to 21-hydroxylase deficiency
A 16 year old girl presents with primary amenorrhea. She began breast development at age 11 years. Pubic hair is Tanner 2. She has a few wispy axillary hairs. On exam, her external genitalia appears phenotypically female but you palpate 2 inguinal masses.
Most likely diagnosis is ____
A 16 year old girl presents with primary amenorrhea. She began breast development at age 11 years. Pubic hair is Tanner 2. She has a few wispy axillary hairs. On exam, her external genitalia appears phenotypically female but you palpate 2 inguinal masses.
Most likely diagnosis is complete androgen insensitivity syndrome
