DSD Flashcards
for how long are gonads biopotential?
until 6-7 weeks gestation
what do the cells in the testes produce?
Sertoli cells
- Mullerian-inhibiting substance (MIS aka antimullerian hormone (MUH)) ⇾ regression of mullerian ducts
Leydig cells
Testosterone and insulin-like peptide 3 (INSL3)
Testosterone ⇾ growth and differentiation of the wolffian ducts, growth of the penis and prostate
INSL3 ⇾ testicular descent
DHT ⇾ growth of prostate and fusion of labioscrotal folds
when do testes descend into the scrotum?
Inguinoscrotal phase (weeks 27 and 35) - androgens
Testosterone and INSL3 mediated
mullerian develops into what
also called what
uterine tubes,
uterus and
upper vagina
paramesonephric
wolffian develops into what
also called what
vas deferens,
epididymis and
seminal vesicles
mesonephric
Endoderm develops into?
Cloaca
develops into
->Anorectal sinus and Urogenital sinus
urogenital sinus develops into:
bladder
urethra
protrate (males)
Mesoderm develops into?
Urogenital ridge which gives rise to:
- ductal system (Wolffian ducts, Mullerian ducts)
- Gonads
Adrenal cortex
Kidneys
Ureters
Ectoderm develops into what
Genital tubercle
Urethral folds
Labioscrotal folds
What do these develop into:
Genital tubercle
Urethral folds
Labioscrotal folds
Genital tubercle
Clitoris/Penis
Urethral folds
Labia minora/penile urethra
Labioscrotal folds
Labia majora/scrotum
how are Leydig cells stimulated?
by hCG from placenta in the first 2 trimesters
by LH in the third trimester
gubernaculum
male:
guides descent of testes into scrotum
female:
guides ovaries/ductal system into pelvis
ovarian ligament
broad ligament
what do Sertoli cells produce and for how long
Sertoli cells continue to produce high amounts of AMH until puberty.
when does masculinization of the external genitalia happen?
how does it begin?
begins during the ninth fetal week in response to DHT
characterized by lengthening of the anogenital distance
Subsequently labioscrotal folds fuse in a dorsal to ventral fashion
what is and what are types of malformative DSD
Defects in the Morphogenesis of the Urogenital Primordia
A. Defective morphogenesis of the Müllerian or Wofflian ducts
- Malformations of the vagina and uterus
- Congenital bilateral absence of the vas deferens (Cystic fibrosis)
B. Defective morphogenesis of the urogenital sinus and the primordia of the external genital
what is Dysgenetic DSD and what are types
= Abnormal Gonadal Differentiation
A. Dysgenetic DSD in 46,XY patients
- if complete, called “pure gonadal dysgenesis” or “agenesis”
B. Dysgenetic DSD in patients with mosaicisms carrying a Y chromosome
1) Ovotesticular DSD
= existence of both testicular tissue and ovarian tissue
2) Asymmetric gonadal differentiation, also known as mixed gonadal dysgenesis
= presence of a more or less dysgenetic testis on one side and a streak on the other
C. Dysgenetic DSD in 46,XX patients
1) Ovotesticular DSD
2) Testicular DSD
- SRY positive or SRY negative
D. Gonadal dysgenesis in sex chromosome aneuploidies
In 46XY dysgenic DSD complete dysgenesis, what is the phenotype?
Genes involved?
the fetus is completely feminized, owing to the lack of the two testicular hormones involved in fetal sex differentiation
SRY mutations, SF1 mutations, WT1 mutations
What is present in ovotesticular DSD?
existence of both testicular tissue, including seminiferous tubules, and ovarian tissue, where the presence of follicular structures containing oocytes is mandatory
may present with bilateral ovotestes—gonads carrying both testicular and ovarian tissue—one testis and one ovary or one ovotestis and one testis or ovary.
**Testicular tissue usually dysgenetic, ovarian tissue normal
Mixed gonadal dysgenesis
- what is it
- most frequent karyotype
- lab to look for it
presence of a more or less dysgenetic testis on one side and a streak on the other.
The most frequent karyotype is 45,X/46,XY, where the predominance of the 45,X on one side explains the development of the streak and the predominance of the 46,XY lineage underlies the development of the testis on the other.
labs: low AMH
what are examples of Gonadal dysgenesis in sex chromosome aneuploidies
Klinefelter
47,XYY, 47 XXX
Turner
Turner syndrome variants
What are types of Non-dysgenetic DSD with Testicular Differentiation
1) Disorders of androgen synthesis
2) Disorders of androgen action: The Androgen Insensitivity Syndrome (AIS)
3) Disorders of AMH synthesis or action
What are examples of Disorders of androgen synthesis
- Leydig Cell Aplasia or Hypoplasia - Defects in LHCG Receptor
- Smith-Lemli-Opitz Syndrome - Defect of Cholesterol Biosynthesis
- Lipoid Congenital Adrenal Hyperplasia - Defects of Pregnenolone Biosynthesis
- P450c17 Deficiency - Defects of Androstenedione and DHEA Biosynthesis
- P450 Oxidoreductase (POR) Deficiency
- 3β-HSD Deficiency - Defects of Δ4-Steroid Biosynthesis
- 17β-HSD Deficiency - Defect of Testosterone Biosynthesis
- 5α-reductase type 2 - Defects of DHT Biosynthesis
- MAMLD1 - Other Defects of Androgen Biosynthesis
Example of Disorders of AMH synthesis or action
persistent Müllerian duct syndrome (PMDS)
what are types of Non-dysgenetic DSD with Ovarian Differentiation
A. Disorders of adrenal steroidogenesis
21-Hydroxylase Deficiency (21-OHD)
11β-Hydroxylase Deficiency
3β-Hydroxysteroid Dehydrogenase Deficiency
B. Glucocorticoid receptor gene mutation
C. Placental aromatase deficiency
D. P450 oxidoreductase deficiency
E. Maternal sources: Androgens and progestogens
def of micro penis?
what does it mean?
Definition:
Stretched penile length < 2.5 cm in full term infant
< 2.0 cm @ 34 weeks;
< 1.5 cm @ 30 weeks
Isolated Micropenis may indicate LH/FSH deficiency -> pituitary deficiency or isolated hypogonadotropic hypogonadism
