10/23 Embryology of male Reproductive Flashcards
what are the Genetic; Gonadal; and Phenotypic traits of a male?
Genetic: 46XX or 46XY; Gonadal: Testis; Phenotypic: Internal ducts and external genitalia
where is the source of the masculinization of the ducts and external genitalia of a male?
the Testes produce adrogens!
Where is the bipotential gonad located in early embryo?
at the genital ridge
what is the composition of the bipotential gonad?
the coelomic epithelium, germ cells, primitive sex cords.
what are the components of the bipotential gonad?
the Germ cells, coelomic epithelium, and the primitive sex chords.
what is the molecular signal that confers competence to teh urogenital ridge, and yealds the bipotential gonad? (both genders)
SF1 and WT1
what reciprocal inhibition is present in the bipotential gonad?
Sox9/Fgf9 and Wnt4/Respondin1 the balance between these keeps the genital ridge in a bipotential state!
what will shift the balance of the bipotential gonad towards a male?
SRY gene on the Y chromosome will give a boost to Sox9/Fgf9 and down reg. Wnt4/Respondin1 and give development as a male.
on the short arm of Y chromosome, encoding 223 AA non-histone protein.
the SRY gene
what if you don’t have the SRY gene?
the gonads will become an ovary.
223 AA non-histone protein coded for on the short arm of the Y chromosome, gene activated by HMG box binding to it and bending the DNA! and is the first gene specific for testis
SRY
when is the SRY gene expressed?
only in genital ridge at the time of testis induction
where would you expect SRY and Sox9 to be expressed
SRY would be At the genital ridge in males, and SOX9 would be expressed at the genital ridge in both females and males in the biopotential gonad… until the female “track” is chosen by over expression of WNT4 and SOX9 would go way down!
what would be the phenotype of an individual with a 46xy genotype who has a null mutation in SRY or Sox9?
they would not have SRY to up reg. sox9 and therefore would choose the female tack of development!
what is the molecular signal that would be expected to lead to a male development?
SRY from the y chromosome expressed and leads to a enhancement of SOX9 expression that down regulates WNT4 (female signal) and up regulates SF1 and Other genes to lead to the development of testes.
what is the molecular signaling (genes) that lead to female development?
WNT4 wins the reciprocal inhibition with SOX9 and expresses DAX1 that down regulates SOX9. WNT4 also leads to other genes (TAFII 105) along with DAX1 that will then lead to Ovaries
what structures develop if SRY upregulates Sox9 instead of ovary follicle cells from the ceolomic epithelium.
you would get male sertoli cells.
in males and females…what does the gonadal ridge develop into?
Sex cords and connective tissue
primitive sex cords grow into the gentital ridge from what tissue origin
the mesonephros.
what will incorporate into the sex cords developing out of the genital ridge from the mesonephros?
the primitive germ cells! from the yolk sack
what will develop from the outer cords in the genital ridge?
the seminiferous tubules and contain sertoli cells
What develops from the deeper cords of the genital ridge?
the rete testis
The develping teste will contact and make efferent ducts with what tubule?
the mesonephric tubules
converts the genital ridge cells tot eh bipotential gonads
SF1
required for Sox 9 expression and upregulated by SRY/Sox9
SF1
promotes testosterone production by leydig cells
SF1
Promotes MIS (AMH) production by sertoli cells
SF1
what is the outline of gonad development in males from the UG ridge?
UG ridge (get SF1 / WT1) develope bipotential gonad (get SRY SOX9) then get testes and then get sertoli cells and Leydig cells (use SF1) to then get AMH (from sertoli) and Testonsterone (from leydig cells)
Sepperate the seminiferous tubules (lie between tubules), near nerves and blood vessels
Interstitial cells of Leydig
Produce testosterone
Leydig cells
Appear during embryo development (masculinize fetus), and then disapear to reapear at puberty.
leydig cells
Located within the seminiferous tubules (to support the spermatogonia)
sertoli cells
Organize testis, secrete MIS (AMH)
Sertoli cells
how does the vas deferens attach to the urethera?
the meonephric duct that will become the vas deferens is attached to the primitive bladder it will move caudally, and the ureter develops off of the mesonephric duct and will then develop seperate entrances with the ureter above and the ductus deferens draped over the ureter, with the vas deferens attaching directly to the urethra.
what is the purpose of the secretion of sertoli cells?
Mullerioan inhibiting substance or Anti-Mullerian Hormone (MIS, AMH) causes the paramesonephric ducts to degenerate.
how do we form the male accessory glands?
they arise as epithelial outgrowths from their associated duct systems.
what accessory glands form from the epithelium of the ductus deferens?
the seminal vesicles
what accessory glands form from the urethra
prostate and bulbourethral gland
what is the required hormonal signal for the development of the accessory glands from the epithelial of the associated ducts?
either testosterone (the epididymus or the seminal vesicle) or dihydrotestosterone (the prostate, and bulbourethral gland, and the penis)
how do we get testosterone from dihydrotestosternoe (enzyme)
5-alpha-reductase.
How do we form the vas or ductus deferens?
testosterone secreted by leydig cells causes mesonephric duct to persist and become the vas deferens
the line of fusion of the urethral folds
the median raphe
what is a incomplete closure of the urethral or genital folds result in in a male?
hypospadias of the glans penis or of the pinile urethra…or a hypospadias elswhere.
describe the devolpment of the external male genitalia from the bipotential gonad
the genital folds zip up to form the shaft in combination with the genital tubercle. The genital swelling becomes the scrotum
what are some defects that can occur in the development of external male genitalia from the bipotential gonad
hypospadias (hole in bottom of penis), epispadias (urethral orifice on the dorsal side of penis)
the urethral orifice on the dorsal side of penis
Epispadias
what are the three phases of testicular descent?
- caudal displacement 2. Transabdominal descent 3. Transinguinal descent
what causes the first phase of the testicular descent
the enlargement of testis and regression of mesonephric kidneys
what causes the transabdominal descent
testes descend to level of inguinal rings, attributed to MIS and regressio of paramesonephric ducts.
what causes transinguinal descent
testes descend to scrotum due to shortening of the gubernaculum testis (inguinal ligament of mesonephros), and testis slides behind the process vaginalis
what biomolcular signal seems to be important for testicular descent?
IGF3
what is cryptorchidism
failure of testis to descend into the scrotum
The process vaginalis fills with fluid
Hydrocele
Process vaginalis should close with testicular maturation but is still a weak point that can open with straining.
Inguinal hernia
how to treat cryptorchidism
administer IGF3
how does the occurance of Cryptorchidism affect morbidity later?
50 X increase in the rate of testicular cancer
what is the comparative time course of male and female development?
the male starts earlier and finishes later.
what is a true hermaphrodites
both testicular and ovarian tissue is present external genitilia female and maybe clitoral hypertrophy. Gonads are mixed and ducts are mixed.
what is the ost common genotype of hermaphrodite
46XX ovotestis is the most common
how could a 46XX lead to true hermaphrodites?
Probably from a fusion of embrio
what is a female pseudohermaphrodites
46XX - Internal structure is female External genitalia is masculinized, Excess production of adrenal and androgens
Adrenal androgens are produced too late to affect gonad and duct development
Adrenogenital syndrome — can include salt wasting and hypertension
there is a great chart on the biomolecules…
PICTURE!!!!
what is a male pseudohermaphrodites
46XY but no SRY or inadequate androgen production by the testes: female gonads and genitilia or persistence of some undescended testes and variable duct formation.
Adrogen insensitivity
“testicular feminizaton” if the no somatic testosterone receptors: female external phenotypes but no internal female organs and persistent testes. (no acne and no axillary hair)
46XY but 5-alpha-reductase derficiency
no Dihydrotestosterone: no full development of external male genital until puberty
46 XY but fail to make MIS
therefore persistence of mullerian duct and uterus and tubes, and cryptorchid since the testes adhere to uterine tubes.
requires testosterone from leydig cells to persist
mesonephric duct
need DHT/5-alpha-reductase
male glands and external genitalia
causes paramesonephric ducts to regress
MIS from the sertoli cells (therefore no uturus)
