Lecture 6: Development of Genitalia Flashcards
What weeks is the embryo considered considered “indifferent”?
Weeks 1-6
What week does sexual differentiation begin?
Week 7
What are the male primoridal germ cells; what week do they arise; and what ‘derm is each from?
- Arise from the epiblast during week 2
- Seroli Cells: from Coelomic Epithelium
- Interstitial (Leydig) cells: from Intermediate Mesoderm
What are the female primoridal germ cells; what week do they arise; and what ‘derm is each from?
- Arise from the epiblast during week 2
- Follicle Cells: from Coelomic Epithelium
- Thecal Cells: from Intermediate Mesoderm
Where do they primoridal germ cells end up after gastrulation and body folding? Explain their migration up until the 6th week.
- Arise from epiblast during week 2
- Migrate through the primitive streak and reside in yolk sac and allantois (endoderm)
- Migrate via dorsal mesentery during the 5th week
- Colonize primary sex cords during 6th week
What is the SRY gene; why is it significant?
- Sex determining Region Y human gene
- These are DNA binding proteins called testis-determining factor (TFD)
- Sex-determining region on the Y chromosome
- If SRY is present you will be male, if absent you will be female
If SRY gene is present what is the cascade of events that occurs in development of a male?
- Causes I.M. to form Leydig Cells which then produce Testosterone causing Mesonephric ducts to persist
- Causes C.E. to become somatic support cells and then Seroli Cells which produce AMH (aka MIF/MIS) which causes Paramesonephric duct degeneration
- DHT will be produced causing the development of Male External Genitalia
If SRY gene is absent what is the cascade of events that occurs in development of a female?
- Causes I.M. to from Thecal cells, which do NOT produce testosterone leading to degeneration of Mesonephric ducts.
- Causes C.E. to form support cells and then Follical cells which do NOT produce AMH so the Paramesonephric ducts persist.
- Estrogen production will lead to the development of Female External Genitalia
What is Ovotesticular DSD?
- True Gonadal Intersex
- Have both testicular and ovarian tissue and an ovotestis
- Phenotype may be male or female, but external genitalia ambigous
What is 46, XX DSD; what causes it; what is commonly seen in this condition?
- Caused by exposure of female fetus to excessive androgens
- Ovaries present, but external genitalia masculanized
- Clitoral hypertrophy, partial fusion of labia majora, and persisten urogenital sinus
- Congenital adrenal hyperplasia (CAH) is common = deficiency is 21-Hydroxylase = reduction in cortiol and excess prod. of androgens
What is 46, XY DSD; the 2 common causes and what’s seen?
- Has testis, but phenotype is female
Caused by:
1) Inadequate production of testosterone and/or AMH (i.e. 5α-reductase deficiency)
2) Androgen insensitivity syndrome (dysf. receptors)
- Testicular development rudimentary to normal and may have persisitent paramesonephric ducts
- External genitalia are female or ambigous
What is the genotype in androgen insensitivity syndrome, normal presentation, and what is seen?
- 46,XY genotype and testes are present
- Normal appearing female external genitalia
- Blind end vagina
- Absent or rudimentary uterus and uterine tubes
- At puberty normal breast development and femal characteristics, but no menstruation.
What will occur if SRY is present, but you have not enough AMH or no AMH?
- Mesonephric ducts and Paramesonephric ducts will BOTH persist so you will have male and female internal genitalia.
- You will have male external genitalia
What will occur if SRY is present and you have a 5α-reductase deficiency (unable to convert testosterone to DHT)?
- Develop male internal genitalia and will have female or ambigous external genitalia until puberty
- At puberty there will be a spike in testosterone and that will lead to masculinization of the genitalia
What is the Coelomic epithelium and what does it give rise to?
- Outer somatic mesoderm lining the urogenital (gonadal) ridge)
- Gives rise to primary sex cords
- Sex cords will be the cortex and medulla of gonads
In males the primary sex cords persist and become what 2 structures?
1) Seminiferous cords
2) Sertoli cells (surface epithelium)
Connective tissue from intermediate mesoderm becomes what 2 things in male gonad development?
1) Leydig Cells
2) Tunica Albuginea
The secondary sex cord arise from what; produce what 2 things in female gonad development?
- Arise from Coelomic epithelium
1) Primordial follicles
2) Graulosa cells
What process produces primordial follicles in female gonadal development?
Active mitosis of oogonia occurs during fetal life producing primordial follicles
Persistence of the Paramesonephric (Müllerian) ducts produces what strucutres?
- Uterine tubes
- Uterus
- Superior part of Vagina
Persistence of the Mesonephric (Wolffian) ducts in males produces what?
- Epididymis
- Vas Deferns
- Seminal Vesicles
- Ejaculatory Ducts
What 2 things to the Mesonephric tubules form in males?
1) Efferent ducts
2) Rete Testis
What are remenants of the Paramesonephric ducts that are sometimes seen in males?
- Appendix testis
- Prostatic utricle
Where are the Paramesonephric ducts located and what do they produce cranial and caudally?
- Located in lateral coelomic bay
- Cranial: uterine tubes
- Caudal: uterovaginal primordium
What are remenants of the degenerated Mesonephric (Wolffian) ducts seen in females?
- Duct of epoöphoron
- Paroophoron
- Gartner’s duct
What forms the sinus tubercle in females; what is the relevance of the sinus tubercle?
- Fused paramesonephric ducts (uterovaginal primordium) contact the urogenital sinus (endoderm)
- This forms the sinus tubercle
- The sinus tubercle induces the formation of the sinovaginal bulbs (endodermal outgrowths), which fuse to form the vaginal plate
What occurs once the vaginal plate is formed?
Epithelium will proliferate and later break down forming the lumen of the vagina (canalization)
Which ‘derm forms the upper and lower portion of the vagina?
Upper: mesoderm
Lower: endoderm
What is the cause of Uterus didelphys, arcuatus, and bicornis?
Failure/incomplete fusion of the paramesonephric ducts
What is the cause of Uterus bicornis unicolis?
Atrophy or atresia of one of the paramesonephric ducts
What leads to Cervical Atresia?
Atrophy of paramesonephric duct at most caudal portion; area of cervix atrophied
What causes Vaginal Atresia?
Failure of the sinovaginal bulbs to form
Embryologically where does the prostate and bulbourethral glands arise from; what does splanchnic mesoderm form?
- Prostate arises from pelvic part of urogenital sinus: endoderm
- Bulbourethral glands arise from the phallic part of urogenital sinus: endoderm
- Splanchnic mesoderm: smooth muscle and CT
What week does the paramesonephric duct degenerate and start to form distinctive characteristics; what week are we fully differentiated?
- Degenerates at week 9
- By week 12 are fully differentiated
- Most clinicians wait until week 20 to actually determine sex of baby
A male under the influence of DHT will cause the genital tubercle, urethral (urogenital) fold, and labioscrotal swellings to form what?
Genital Tubercle:
- Glans Penis
Urethral (urogenital) folds:
- Lateral walls of urethra
- Spongy urethra
- Penile raphe
Labioscrotal swellings:
- Scrotum
A female under the influence of estrogen will cause the genital tubercle, urethral (urogenital) fold, and labioscrotal swellings to form what?
Genital Tubercle:
- Glans Clitoris
Urethral (urogenital) folds:
- Fenulum of labia minora
Labioscrotal swellings:
- Labium Majus (Majora)
- Mons pubis
What ‘derm is the spongy urethra made of and how do we get spongy urethral completion; forms the?
- Spongy urethra is endoderm, but does not quite make it all the way to end of penis
- We need ectoderm to proliferate (external urethral orifice) and go down to meet up with spong urethra (endoderm)
- This will form our navicular fossa
How can we account for Glanular, Penile, and Penoscrotal Hypospadias embryologically?
Glanular: navicular fossa did not migrate correctly; opening of glans penis on ventral side
Penile: opening in the shaft of penis due to urogenital fold not fusing
Penoscrotal: failure of the labioscrotal folds to fuse
What is Epidpadias and what is it commonly associated with?
- Improper location of genital tubercles to cloacal membrane
- Associated with ectopic vesicase/exstrophy of the bladder
The suspensory ligament houses what; where does the ovarian ligament arise from?
- Houses the Ovarian artery
- Cranial part of gubernaculum
Where does the round ligament of the uterus arise from?
Caudal part of gubernaculum
How is the broad ligament formed and what does it separate?
- Midline fusion of paramesonephric ducts brings along a peritoneal fold
- Separates pelvic cavity into: Rectouterine pouch and Vesico-uterine pouch
What does the urogenital sinus form in males vs. females?
Males: bladder, urethra (prostatic, spongy), prostate gland, bulbourethral gland
Females: bladder, urethra, inferior vagina, greater/lesser vestibular glands, vestibule, hymen
******ALL from endoderm!****
