Development of the Reproductive system Flashcards
Timeline for the reproductive system development
Weeks 1-6: indifferent embryo
Week 7: sexual differentiation begins
week 12: Female and male genitalia can be recognized
week 20: Phenotypic differentiation complete
what are the primordial germ cells and their characteristics
Progenitor cells of the oogonia and spermatogonia
Primordial germ cells are specified within the epiblast
after gastrulation and body folding, primordial germ cells end up within the yolk sac wall
Primordial germ cells migrate up the dorsal mesentary of developing gut to enter the genital ridge of the intermediate mesoderm in week 5
what happens in the indifferent gonad during week 6
Primitive gonads appear initially as pair of longitudinal swellings in the urogenital ridges of the intermediate mesoderm at about axial level T10
formed by proliferation and delamination of coelomic epithelium and condensation of underlying mesenchyme
Primordial germs stimulate the proliferation and delamination of cells from the coelomic epithelium of the genital ridge to form the somatic support cells (primitive sex cords)
What do the somatic support cells differentiate into in males and females?
Males the somatic support cells become the sertoli cells
in females they become the follicle cells
what are the two sets of reproductive ducts that form eary in development?
Mesonephric tubules and mesonephric duct:
-these tubules and ducts form within the urogenital ridge and serve as early collecting ducts for the mesonephric kidney. Mesonephric ducts open into the urogenital sinus
Paramesonephric (mullerian) ducts
- new ducts form on both sides from an invadignation along the anteriolateral surface of the urogenital ridge
- cranially they open to the coelomic cavity and caudally they meet with each other when attaching to the urogenital sinus
What is critical for sexual dimorphism
the key to sexual dimorphism is the Y chromosome
this chromosome contains the testis determining factor gene SRY
presence or absence of this factor has a direct effect on gonadal differentiation and acts as a switch to initiate a cascade of many downstream genes that determine the fate of rudimentary sexual organs
in the absence of it the development is female
Development of the testis
SRY gene is transcribed on days 42-52 which then turns on the gene expression for SOX9 in somatic support cells and suppresses WNT4 (pro-female gene)
Sertoli cells surround the primordial germ cells, and on the 4th month with the sertoli, germ, and myoepithelial cells they organize into the testis cords and eventually develop into the seminiferous tubules
The testis cords become connected to the rete testis and the rete testis becomes connected to the efferent ductules (remnants of mesonephric tubules) thereby linking the testis cords to the developing epididymis and vas deferens (mesonephric duct)
Primordial germ cells proliferate and differentiate into Type A spermatogonia 3 months postnatal
what does a subset of intratubular cells differentiate into?
Leydig cells that are recruited by the sertoli cells
the leydig cells begin producing testosterone during the 9-10th week and begin influencing differentiation of genital ducts and external genitalia
What happens to the paramesonephric ducts at week 8-10
The seroteli cells express anti-Mullerian hormone (AMH) or also known as Mullerian inhibitor substance that drives the regression of paramesonephric ducts at week 8-10
the remenants of paramesonephric duct in males include appendix testis and prostatic utricle
what does the Leydig cell derived testosterone drive to form?
Leydig cell derived testosterone drives the mesonephric tubules to form:
- Effernt ductules: paradidymis
- Epididymis
- Vas deferens
- Seminal vesicle
what is the importance of DHT
a portion of testosterone is converted to duhydrotestosterone (DHT) by 5a reductase
this is important for driving the development of the external genitalia (penis, scrotum, prostate, testicular descent)
How do seminal vesicles form?
Seminal vesicle formed from the buds emanating from the mesonephric duct, hence they are derived from intermediate mesoderm of urogenital ridge
how does the gland form?
forms from buds emanating from endoderm of urogenital sinus within future membranous region of the pelvic urethra (week 10)
how does the bulbourethral glands form?
also from the endoderm buds of urogenital sinus
Development of genital tubercle?
Ectodermal covered mesodermal swelling at the ventral end of the phallic portion of the urogenital plate
how extensive it outgrows depends on the DHT levels
development of the Urogenital plate and what forms ventral to it?
With rupture of the cloacal membrane, the floor of the phallic segement of the urogenital sinus is lost
where as the roof of the phallic segment expands along the lower surface of the genital tubercle
-as the genital tubercle enlarges this endodermal extension will form the urogenital plate
A urethral groove forms along the vental surface of the urogenital plate as the genital tubercle elongates
distally the urethral groove and urogenital plate terminate at the solid glans plate
what do the urogenital folds form?
A pair of swellings called the urogenital folds (or cloacal folds) develop on either side of the urogenital plate through an expansion of mesoderm underlying the ectoderm
at the distal end of the urogenital folds, remenants of the cloacal membrane adjacent to the genital tubercle remain as the glans plate
a new pair of swellings, the labioscrotal swellings will appear on either side of the urethral folds
Development of the male external genitalia
Initially the urethral groove and urogenital folds extend part of the way along the shaft of the elongating phallus
As the phallus and urogenital plate continue to elongate the urogenital folds grow toward one another and fuse in the midline beginning proximally in the perineal region and extending distally toward the glans penis
-this converts the urethral groove into the tubular penile urethra
Solid glans plate canalizes and joins the developing penile urethra to form the glans urethra and external penile meatus
What drives the legthening and growth of the genital tubercle or labioscrotal swellings forming the scrotum?
DHT
How do the testis descent?
Suspensory ligament contains gonadal vessels, nerves, and lymphatics and connections are made at T 10
the gubernaculum which is a structure connecting the gonad to base of the labioscrotal swellings will shorten eventually pulling the testes into the scrotum
What is it called if the testis fail to descend?
Failure to descend leads to cryptorchidism
most self resolve within a year but must be watched as incidence of testicular cancer is greatly increased
what is Hypospadias and Epispadias
Hypospadias is the most common male birth defect after cryptorchidism
-due to failure of urethral folds to close properly
Epispadias: uretra on top of the penis, cause is unknown but may be due to improper ventral body closure or formation of too large of a cloacal membrane to be covered when it ruptures
How does the ovary initiate its differentiation?
In the absence of the SRY gene, somatic support cells express WNT4 and FOXL2
FOXL2 continually suppresses SOX9 expression thereby maintaining female gonad differentiation
Primordial germ cells differentiate into the oogonia, proliferate ad differentiate into oocytes
the developing oocytes induce the surrounding somatic support cells to become follicular cells
the follicle cells surrounding individual oocytes are responsible for arresting the primary oocyte in prophase I of meiosis until puberty
what are the duct system in females
Since no Sertoli cells the Paramesonephric ducts are retained
absence of Leydig cells the mesonephric duct system is lost
-remnants include epoophoron and paraoophoron near the ovary and gartners cyst
the Paramesonephric duct will fuse at week 9-10 at the inferior proximal end and form the uterus and the un-fused portion forms the uterine tubes
what are some uterus anomalies?
all due to improper or failed fusion of paramesonephric ducts
- Didelphys: double uterus
- Bicornate: two bodies one cervix
- Double uterus and double vagina
- Double uterus
- Unicornate uterus: only one uterine tube formed
- sepated uterus
Formation of the Vagina
Contact of paramesonephric duct to urogenital sinus stimulates proliferation and formation of sinuvaginal bulb (endodermal thickening)
Sinuvaginal plate will proliferate and lengthen and is eventually canalized
The entire vagina with possible exception of the upper vagina fornix is derived from endoderm
Vaginal agenesis?
due to failure of normal sinuvaginal bulb development or canalization or due to agenesis of the parasmesonephric ducts
Female external genitalia developmen
Phallic segment of urogenital sinus has a urogenital plate, glans plate, and genital tubercle
in the absence of testosterone and DHT, there is no lengthening of genital tubercle and no fusion of urogenital folds or labioscrotal swellings
the urogenital folds in female form the labia minora
labioscrotal folds in female form the labia majora
differential growth and expansion separates the urethra from the vaginal opening
Formation of broad ligament
MIdline fusion of paramesonephric ducts drags the lower urogenital ridge, which is covered with developing peritoneum into the pelvic cavity
with completion of uterus and uterine tube development, the remaining tissue thins and forms a double peritoneum fold that supports the uterus and the ovary
How does the descent of the ovary occur and what makes up those structures associated with the process
Descent of the ovary: it has a suspensory ligament superiorly containing vessels, nerves, and lymphatics
also has a gubernaculum connecting the gonad to the labioscrotal swelling, the gubernaculum becomes attached to developing uterus restricting the furthur ovarian descent
Round ligament of ovary is the portion of gubernaculum between the gonad and uterus
Round ligament of uterus is the portion of the gubernaculum between the uterus and base of labioscrotal swellings (future labia majora)
17B Hydroxysteroid dehydrogenase deficiency
inadequate testosterone synthesis
17B hydroxysteroid dehydrogenase is important for converting androstenedione to testosterone
has testes but phenotype appears female
Androgen insensitivity syndrome
Loss of functional androgen receptors: X linked recessive
Have testes but no spermatogeneis, testosterone levels may be elevated due to lack of negative feedback
At puberty, the testosterone is metabolized to estradiol initiating female secondary sexual characteristics
They produce AMH so the paramesonephric system is suppressed resulting in the absence of a uterus or uterine tubes and the vagina is short and ends blindly
Testis usually found in inguinal or labial regions increasing risk of tumor formation in the gonads
5alpha-reductase deficiency
inability to convert testosterone to DHT, autosomal recessive
Normal testis and duct system development as there is AMH and testosterone
however there is underdeveloped male external genitalia, the gdegree of which depends on level of deficiency of DHT but they can exhibit an external female phenotype
Mutation in AMH or AMH receptor
retention of paramesonephric ducts so individual has a uterus and uterine tubes along with male ducts and external genitalia
Congenital adrenal hyperplasia
XX DSD
mutation in genes involved in adrenocortical steroid biosynthesis such as deficiency in 21-hydroxlase leading to excess ACTH production causing adrenal hyperplasia and excessive production of androgens
have ovaries but female genitalia is masculinization and depending on androgen levels can exhibit fusion of labioscrotal swellings and an enlarged clitoris with what may look like hypospadias
Ovotesticular disorders
Have both testicular and ovarian tissue
-karyotype is 46XX
AMbiguous external genitalia or predominatly female
Usually have a uterus
Causes:
- translocation of piece of Y chromosome onto X chromosome (barr body causes mosaicism)
- subset of cells may have mutation in Y chromosome
- anomaly in sex determination and differentiation of primordial germ cells
What is the male and female structure based on the presumptive rudiments: Indifferent gonad
Testis
Ovary
What is the male and female structure based on the presumptive rudiments: Primordial germ cell
Spermatogonia
Oocyte
What is the male and female structure based on the presumptive rudiments:Somatic support cell
Sertoli cell
Follicle cell
What is the male and female structure based on the presumptive rudiments: Stromal cell
Leydig cell
Thecal cell
What is the male and female structure based on the presumptive rudiments: Gubernaculum
Gubernaculum testis
Round ligament of ovary
Round ligament of uterus
What is the male and female structure based on the presumptive rudiments: MEsonephric tubules
Effernt ducts of testis
Paradidymis
Epoophoron
Paroophoron
What is the male and female structure based on the presumptive rudiments: Mesonephric duct
Appendix of Epidiymis Epididymis Vas deferens Seminal vesicle Ejaculatory duct
Appendix vesciculosa
Duct of epoophoron
Gartners duct
What is the male and female structure based on the presumptive rudiments: Paramesonephric duct
Appendix of testis
Fallopian tubes
uterus
vagina
What is the male and female structure based on the presumptive rudiments: Urogenital sinus
Prostatic and membranous urethra
prostatic utricle
prostatic gland
Bulbourethral glands
Membranous urethra
Urethral/paraurethral glands
greater vestibular glands
What is the male and female structure based on the presumptive rudiments: Genital tubercle
Glans penis
corpus cavernosa of penis
corpus spongiosum of penis
glans clitoris
corpus cavernoisa of clitoris
bulbospongiosum of vestibule
What is the male and female structure based on the presumptive rudiments: Urogenital folds and urogenital and glans plate
Penile urethra/ventral part of penis
Labia minora
What is the male and female structure based on the presumptive rudiments: Labioscrotal folds
Scrotum
Labia majora
