Embryo Of Genital System Flashcards
What happens during weeks 1-6 for genital system of embryo?
Remains in an undifferentiated state
What happens at week 7 for the genital system of embryo?
phenotypic sexual differentiation begins
What happens at week 12 for genital system of embryo?
Male and female external genitalia can be recognizd
What happens at week 20 for genital system of embryo?
phenotypic differentiation complete
Where are primordial germ cells derived from, and where do they go?
From endoderm of yolk sac
Invade dorsal mesentery and migrate to urogenital ridges
What guides the migration of the primordial germ cells?
C-kit receptor
Stem-cell factor (c-kit ligand) on PGCs
What happens when primordial germ cells fail to reach genital ridges?
Gonadal dysgenesis
Describe pure gonadal dysgenesis (PGD)
a normal set of chromosomes but nonfunctional gonads
Normal karyotype but may have defects of a specific gene on chromosome
Swyer syndrome PGD 46 XY
XX gonadal dysgenesis PGD 46 XX
Describe gonadal dysgenesis that results from missing all or part of second sex chromosome
Turner syndrome (45 X) 46XY/45X
What are primary sex cords? Describe the gonad at this point
Aggregates of supporting cells (hormone secreting cells)
Gonad now has an outer cortex and inner medulla
What ducts play the most important role for male genital development?
Mesonephric ducts
What ducts play the most important role in female genital development?
Paramesonephric ducts
Describe fetal sex development
Encoded on sex-determining region of Y-chromosome (SRY)
Synthesis of SRY protein (testis-determining factor, TDF) triggers male development
If not expressed (absent of defective), female path is followed
Female: basic (default) development pathway
What is SOX9?
Transcriptional regulator for testes differentiation vis steroidogenic factor 1 or SF1
What is the transcriptional regulator for testes differentiation?
SOX9 via SF1
What is required for proper sexual differentiation and chrondrogenesis?
SOX9
What results from a mutation in SOX9?
Campomelic dysplasia
What is campomelic dysplasia?
Mutation in SOX9
Rare autosomal dominant congenital short limbed dwarfism
Characterized by congenital bowing of long bones associated with skeletal and extra skeletal features like hypoplastic lungs, malformations of cervical spine, heart, and kidneys
Characteristic feature is male t female sex reversal
Almost fatal outcome
Describe the progression to regression of paramesonephric ducts in males
Activation of SRY gene
TDF -> Differentiation of bipotential gonad into testis
SOX9 via SF1 -> Sertoli Cell differentiation
Mullerian inhibitory substance (anti-Mullerian hormone or Mullerian inhibitory factor)
Regression of paramesonephric (Mullerian) ducts
Describe the production of testosterone in male
Activation of SRY gene
TDF -> Differentiation of bipotential gonad into testis
SOX9 via SF1 -> Interstitial (Leydig) cell differentiation
Steroid synthesis
Testosterone -> 5alpha-reductae-Dihydrotestosterone
What does dihydrotestosterone do?
Influences differentiation of external genitalia and development of prostate
Where is 5-alpha-reductase I made?
Liver and skin
Where is 5-alpha-reductase II made?
By parts of male reproductive tract (epididymis, seminal vesicle, prostate)
Which enzyme is deficient in 5 ARD (->intersexuality)?
5-alpha-reductase II
What effect does testosterone have on mesonephric ducts?
Influences differentiation into ductus deferens and epididymis
What hormone influences the masculinization of the mesonephric ducts?
Testosterone
What effect does DHT have on urogenital sinus?
Closes urethra and prostate
What hormone influences the urogenital sinus to close urethra and prostate?
DHT
What does DHT do to genital tubercle?
Masculinizes it into a penis
What hormone influences the genital tubercle to become the penis?
DHT
What effect does DHT have on labioscrotal swellings?
Closes scrotum
What hormone acts on labioscrotal swellings to close the scrotum?
DHT
Describe the primary and secondary cords for the development of the ovaries
Primary (medullary) cords degenerate by 10th week
Secondary (cortical) cords develop and are invaded by primoridal germ cells
Cords form groups of primordial follicles (oogonium and follicular cells)
In females, the mesonephric ducts degenerate except for what?
Epoophoron and paroophoron found in mesentery of ovary
Portions may exist as Gartner’s duct
Describe the persistence of the paramesonephric duct
WTN4 (which also regulates other genes that control ovarian developmet) upregulates DAX1
DAX1 suppresses SOX9 and AMH expression
What suppresses SOX9 and AMH expression?
DAX1 (which is upregulated by WTN4)
Describe relationship between DAX1 and SRY
DAX1 is found on X chromosome in both sexes
SRY expression represses DAX1 expression
DAX1 duplicated in male prevents testis formation, resulting in a 46XY female
Describe development of Paramesonephric ducts
Develop during 6th week as invaginations of epithelium lateral to mesonephros
Cranial end opens into peritoneal cavity
Distal ends join to form uterovaginal primordium (connects to urogenital sinus)
Inhibited in male by AMH secreted by Sertoli cells
What do the paired portions of paramesonephric ducts become?
Uterine tubes
Uterine tubes develop from what?
Paired portions of paramesonephric ducts
What does the uterovaginal primordium become?
Epithelium and glands of uterus
Epithelium of upper 1/3 of vagina
Muscular wall of vagina
What do the epithelium and glands of uterus, epithelium of upper 1/3 of vagina, and muscular wall of vagina develop from?
Uterovaginal primordium
What does the inferior portion of the vagina develop from?
Posterior wall of the urogenital sinus (urinary bladder & urethra)
What is Mullerian (paramesonephric) agenesis?
Failure of paramesonephric ducts to develop
Results in missing uterine tubes, uterus, and variable malformations of upper portion of vagina
Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH)
What causes hematosalpinx?
Retrograde passage of blood into uterine tubes
Can lead to endometriosis and adhesion formation
Cloaca divides into __ and __
Urogenital sinus
Rectum
Urorectal septum divides cloacal membrane into __ and __
Urogenital membrane
Anal membrane
What do urogenital and anal membranes form?
Sphincter urethrae and external anal sphincter
Also forms urethral folds anteriorly and folds posteriorly
Describe development of male external genitalia
Enlargement of genital tubercle forms phallus
Urethral folds become urethral groove, then fuse to form penile urethra
Labioscrotal swellings become scrotum
Describe development of female external genitalia
Genital tubercle elongates and bends inferiorly to become clitoris
Urethral folds become labia minora
Labioscrotal swellings become labia majora
Urethra and vagina open into vestibule
What is cryptorchidism?
Unilateral or bilateral agenesis
Undescended testes. Testes usually descend within first year
Associated with increased incidence of testicular CA
Ectopic testes or ovary (rare)
What is the term for undescended testes?
Cryptorchidism
What s hypospadias?
Incomplete fusion of urethral folds
Urethra opens onto ventral aspect of penis
Can result from inadequate androgen production or inadequate receptor sites for DHT
What is incomplete fusion of urethral folds with the urethra opening on the ventral aspect of the penis?
Hypospadias
What is epispadias?
Urethral meatus opens on dorsum of penis
Often occurs with bladder exstrophy
What is the term for urethral meatus opening on dorsum of penis that often occurs with bladder exstrophy?
Epispadias
Describe Klinefelter syndrome
47 XXY
Small testes, low levels of testosterone
Poorly developed secondary sexual characteristics and gynecomastia
Risk for osteoporosis, 20x increased risk of breast cancer
Elongate limbs
Testosterone replacement therapy
Name the disorder. 47 XXY. Small testes, low levels of testosterone, poorly developed secondary sexual characteristics and gynecomastia, risk for osteoporosis, 20x increased risk of breast cancer, elongate limbs, testosterone replacement therapy
Klinefelter syndrome
Describe Turner’s syndrome
45X
Short stature, no adolescent growth spurt, broad chest, webbed neck, congenital heart disease
Ovary development is abortive
Secondary sex characteristics do not develop
Growth hormone and estrogen replacement therapy
Name the disorder. 45X. Short stature, no adolescent growth spurt, broad chest, webbed neck, congenital heart disease. Ovary development is abortive. Secondary sex characteristics do not develop.
Turner’s syndrome
Describe pseudointersexuality, 46 XX DSD, 46 XY DSD
External genitalia of one sex accompanies gonads of other sex
Describe mechanism of 46 XX DSD
Induced by prenatal exposure to androgens
Exposure after 12th fetal week leads only to clitoral hypertrophy
Exposure at progressively earlier stages of differentiation leads to retention of urogenital sinus and labioscrotal fusion
If exposure occurs sufficiently early, labia will fuse to form a penile urethra
Describe classic virilizing adrenal hyperplasia (46 XX DSD)
Female intersex
Females with severe forms of adrenal hyperplasia have ambiguous genitalia at birth due to excess adrenal androgen production in utero
Ambiguous genitalia ranges from complete fusion of labioscrotal folds and phallic urethra to only cltiromegaly, parial fusion of labiascrotal folds, or both
No abnormalities of ovaries
Name the disorder. Female intersex (46 XX DSD) with ambiguous genitalia at birth due to excess adrenal androgen production in utero
Classic virilizing adrenal hyperplasia
Describe androgen insensitivity syndrome (AIS), 46 XY DSD
X-linked disorder in which receptors remain unresponsive to androgens
Despite normal levels of testosterone, male fetus fails to masculinize
External genitalia are feminine. Internally, they possess non-functioning undescended testes
At puberty, secondary female sexual characteristics may appear due to estradiol from testosterone aromatization
Name the disorder. X-linked disorder in which receptors remain unresponsive to androgens. Despite normal levels of testosterone, male fetus fails to masculinize. External genitalia are feminine, while testes are undescended and non-functional. At puberty, secondary female sexual characteristics may appear due to estradiol from testosterone aromatization.
Androgen insensitivity syndrome (AIS)
46 XY DSD
Describe 5-alpha reductase deficiency (5-ARD)
46 XY DSD
Autosomal recessive condition resulting in inability to convert testosterone to more physiologically active DHT
Genetic males with 5-ARD are born with ambiguous genitalia (underdevelopment of penis & scrotum or pseudovaginal perineoscrotal hypospadias)
Derivative of mesonephric duct are normal
Often misdiagnosed as AIS
Name the disorder. Autosomal recessive condition resulting in inability to convert testosterone to more physiologically active DHT. Genetic males have ambiguous genitalia but normal derivatives of mesonephric duct.
5-alpha reductase deficiency
When is the genotype of the embryo (46 XX or 46 XY) established?
At fertilization