Embryology of the Reproductive System Flashcards
How is genetic sex determined?
- genetic sex is determined at fertilisation by the sperm
- the SRY (sex-determining region of the Y chromosome) gene initiates production of Testis-determining factor (TDF)
- if there is no Y chromosome, there is no TDF and female development commences
What is the reproductive system derived from?
intermediate mesoderm
- the intermediate mesoderm gives rise to the urogenital ridge
- the urogenital ridge gives rise to the urinary system and reproductive system
How do the gonads first appear?
What type of cell appears in the gonads?
- gonads appear as a pair of longitudinal ridges (genital / gonadal ridges)
- gonadal ridges are formed by proliferation of the epithelium and condensation of the underlying mesenchyme
- the germ cells** do not appear in the genital ridges until **week 6
Where do primordial germ cells originate?
When do they enter the genital ridges?
- PGCs originate in the epiblast and migrate through the primitive streak
- they arrive at the primitive gonads at the beginning of week 5 and invade the genital ridges in week 6
- if PGCs fail to reach the genital ridges, the gonads do not develop
What is meant by the indifferent gonad?
How and when does this develop?
- shortly before and during arrival of the PGCs, the epithelium of the genital ridge proliferates and penetrates the underlying mesenchyme
- the epithelial cells form irregularly shaped cords - the primititve sex cords
- in male and female embryos, the cords are connected to surface epithelium
- at this stage (weeks 5-6) it is impossible to determine between the male and female gonad so it is the “indifferent gonad”
How can the indifferent gonad be split into 2 different regions?
- the indifferent gonad can be split developmentally into 2 distinct regions:
- outer cortex
- inner medulla
- the fate of medullary and cortical regions is dependent on TDF production
What is formed from the primitive sex cords if an embryo is genetically male?
What is carried by the PGCs?
- the PGCs carry an XY sex chromosome complex
- under the influence of the SRY gene on the Y-chromosome, which encodes TDF, the primitive sex cords continue to proliferate and penetrate deep into the medulla
- they form the testis** or **medullary cords
Following formation of the medullary cords, what else develops in pursuit?
Rete testis:
- towards the hilum of the gland, the cords break up into a network of tiny cell strands
- these will later give rise to the tubules of the rete testis
Tunica albuginea:
- this is a dense layer of fibrous connective tissue that separates the medullary cords from the surface epithelium
What happens to the testis cords in the 4th month?
What cell types are they composed of at this stage?
- the testis cords become horseshoe-shaped
- their extremities are now continuous with those of the rete testis
- the cords are composed of primitive germ cells and Sertoli cells
- Sertoli cells are derived from the surface epithelium of the gland
What cell type lies between the testis cords?
When do they begin development and what is their function?
interstitial cells of Leydig
- they are derived from the mesenchyme of the gonadal ridge
- they begin development shortly after onset of differentiation of the testis cords
- by week 8, they begin production of testosterone
- the testis is able to influence sexual differentiation of the genital ducts and external genitalia
What happens to the testis cords at puberty?
What does this structure enter and join with?
- testis cords remain solid until puberty, when they canalise to form the seminiferous tubules
- the seminiferous tubules join the rete testis tubules, which in turn enter the ductuli efferentes
- these are the remaining parts of the excretory tubules of the mesonephric system
- the ductuli efferentes link the rete testis and the Wolffian (mesonephric duct), which becomes the ductus deferens
What happens to the primitive sex cords in female embryos?
- female embryos have an XX chromosome complex and no Y chromosome
- the primitive sex cords dissociate into irregular cell clusters, which contain groups of primitive germ cells
- the cell clusters occupy the medullary part of the ovary
- later on they disappear and are replaced by a vascular stroma that forms the ovarian medulla
What happens to medullary cords in a female embryo?
What type of cord develops?
- the medullary cords degenerate
- the surface epithelium continues to proliferate (unlike in males) and gives rise to cortical cords in week 7
- cortical cords penetrate the underlying mesenchyme but remain close to the surface
What happens to the cortical cords in month 3?
What is formed at the end of this process?
- the cortical cords split into isolated cell clusters
- cells in the clusters continue to proliferate and begin to surround each oogonium with a layer of epithelial cells - follicular cells
- the oogonia and the follicular cells together constitute a primordial follicle
What is the difference in the structures that develop and regress depending on whether the spermatocyte carries an X or Y chromosome?
In presence of Y chromosome (44 + XY):
- medullary cords develop
- there are no cortical cords
- there is a thick tunica albuginea
In absence of Y chromosome (44 + XX):
- medullary cords degenerate
- cortical cords develop
- there is no tunica albuginea
During which week do the gonads become distinguishable?
the male and female gonads become distinguishable at 7 weeks
At the stage of the indifferent gonad, what pairs of genital ducts are present?
- both male and female embryos initially have 2 pairs of genital ducts:
- mesonephric (Wolffian) ducts
- paramesonephric (Müllerian) ducts
- the paramesopnephric duct arises as a longitudinal invagination of epithelium on the anterolateral surface of the urogenital ridge
- cranially, the duct opens into the abdominal cavity with a funnel-like structure
- caudally, it comes into contact with the paramesonephric duct from the opposite side in the midline
- the 2 ducts project into the posterior wall of the urogenital sinus to form the sinus tubercle (small swelling)
- the mesonephric ducts open into the urogenital sinus on either side of the sinus tubercle
What is the fate of the genital ducts in the male?
What hormones / substances drive these changes?
Sertoli cells:
- secrete anti-Müllerian hormone (AMH) which suppresses development of the paramesonephric ducts
- a small portion of the paramesonephric ducts remain as the appendix testis
Leydig cells:
- secrete testosterone which stimulates development of the mesonephric ducts, which will go on to form:
- efferent ductules
- epididymis
- vas deferens
- seminal vesicles
- dihydrotestosterone stimulates development of the external genitalia, including growth of the penis, scrotum and prostate
What happens to the genital ducts in the female?
What structures do they go on to form?
- in the presence of oestrogens (maternal and placental sources) and absence of AMH and testosterone…
- the paramesonephric ducts are stimulated and go on to form:
- uterine tube
- uterus
- upper portion of the vagina
- the external genitalia are stimulated:
- labia
- clitoris
- lower portion of vagina
At the indifferent stage, what does the external genitalia consist of?
- in week 3, mesenchyme cells migrate around the cloacal membrane to form a pair of elevated cloacal folds
- cranial to the cloacal membrane, the folds unite to form the genital tubercle
- caudally, the folds are subdivided into urethral folds and anal folds
- the genital swellings appear on either side of the urethral folds
- these will go on to form the scrotal swellings and labia majora
Under the influence of androgens, what happens to the genital tubercle?
- the genital tubercle is now called the phallus
- it rapidly elongates and pulls the urethral folds forwards so that they form the lateral walls of the urethral groove
- the urethral groove extends along the caudal aspect of the phallus but does not reach the glans (most distal part)
- the epithelial lining of the groove forms the urethral plate
How are the penile urethra and external urethral meatus formed?
- at the end of month 3, the 2 urethral folds close over the urethral plate to form the penile urethra
- the penile urethra does NOT extend to the tip of the phallus
- the most distal portion of the urethra is formed in month 4 when ectodermal cells from the tip of the glans penetrate inwards and form a short epithelial cord
- the cord later obtains a lumen to form the external urethral meatus
Under the influence of oestrogens, how do the genital tubercle and genital swellings develop?
- the genital tubercle elongates only slightly to form the clitoris
- the urethral folds do not fuse and develop into the labia minora
- the genital swellings enlarge to form the labia majora
How are the testes pulled towards the deep (internal) inguinal ring?
How long do they reside here for?
- the extra-abdominal gubernaculum shortens and pulls the testes towards the anterior abdominal wall in weeks 7-12
- the testes arrive at the deep (internal) inguinal ring and remain here from 3rd to 7th month
What is the inguinal canal formed by?
- the inguinal canal is formed by the processus vaginalis
- this is an invagination of the parietal peritoneum
What happens to the testes during month 7?
What aids this process and what happens by month 9?
- the gubernaculum begins to shorten again, which pulls the testes through the inguinal canal of the abdominal wall
- this process is aided by pressure from growing abdominal organs
- the testes reach the scrotum by month 9, just before birth
- within the 1st year, the processus vaginalis obliterates and leaves a remnant around the testes called the tunica vaginalis
What 3 muscles make up the abdominal wall?
Where are the deep and superficial inguinal rings located?
- transversus abdominis (and transversalis fascia)
- internal oblique
- external oblique
- the deep ring is the entrance to the inguinal canal and is located in the transversalis fascia
- the superficial ring is the exit of the inguinal canal and is located in external oblique
As it passes through the abdominal wall, how does the testis become ensheathed in layers and what do these go on ot form?
- the testes are accompanied by peritoneal layers derived from the processus vaginalis
- as they descend, they become ensheathed in layers derived from the anterior abdominal wall:
- the transversalis fascia forms the internal spermatic fascia
- the internal oblique muscle forms the cremasteric fascia and muscle
- the external oblique muscle forms the external spermatic fascia
- the transversus abdominis does not contribute a layer as it arches over this region and does not cover the path of migration
What can happen if there is a patent processus vaginalis?
- parts of the processus vaginalis may remain unfused, resulting in formation of small cysts
- the cysts can produce fluid and swell, resulting in hydrocele
- if the processus vaginalis remains open to the abdominal cavity, intenstines may protrude through the inguinal canal and produce an indirect inguinal hernia
How can hydrocele be easily recognised?
What are the symptoms and treatment?
- as the hydrocele is formed by clear fluid, light passes through it easily (transillumination)
- solid tissue of a tumour or hernia would block the light
- hydrocele is benign but larger ones may cause discomfort
- they can be removed surgically
What is cryptorchidism and how common is it?
Why does it occur?
- in 97% of cases, the testes are present in the scrotum before birth
- in most of the remainder, descent will happen in the first 3 months postnatally
- in <1% of infants, one or both of the testes will fail to descend - this is cryptorchidism
- it may be caused by decreased androgen (testosterone) production
What is the treatment for cryptorchidism?
What is it associated with?
- those that remain undescended are surgically corrected at 4-6 months
- the undescended testes fail to produce spermatozoa, so it is associated with infertility
- it is associated with a 3-5% incidence of renal anomalies and increased risk of testicular cancer
How do the ovaries descend during development?
- the ovaries descend to the pelvic brim
- the gubernaculum passes through the inguinal canal to insert onto the labia majora
- it persists in the adult as the ovarian ligament proper and the round ligament of the uterus
What is produced by Sertoli cells and what does this result in?
- Sertoli cells secrete anti-Müllerian hormone (AMH) which causes degeneration of the paramesonephric ducts
- Sertoli cells differentiate under the influence of TDF, which is encoded for by the SRY gene
Differentiation of what cell type is influenced by Sertoli cells?
What is produced by these cells?
- Sertoli cells cause differentiation of the mesoderm of the gonad into Leydig cells
- Leydig cells produce testosterone
- testosterone promotes the maintenance and further development of the mesonephric ducts
What are the derivatives of the mesonephric duct in the male?
- efferent ductules
- epididymis
- vas deferens
- seminal vesicle
What do parts of the paramesonephric duct persist as in the male?
- appendix testies
- prostatic utricle
What drives development of the female genital ducts?
- development of the female genital ducts occurs in the absence of the SRY gene
- as there is no anti-Müllerian hormone, the paramesonephric ducts remain
- as there is no testosterone, the mesonephric ducts degenerate
How can the paramesonephric duct be divided in the female?
What structures are derived from it?
- the paramesonephric duct can be divided into 3 parts:
- cranial part
- horizontal part
- caudal part
- the cranial and horizontal parts become the uterine tubes
- the caudal parts fuse together to form the uterine canal
What are the remnants of the mesonephric duct in the female?
- epophoron
- paraoophoron
- Gartners cyst
How is the urogenital sinus involved in the formation of the vagina?
- the cloaca divides into the anus and the urogenital sinus
- the solid tip of the paramesonephric ducts contacts the urogenital sinus and 2 solid evaginations grow out from the pelvic part of the sinus - the sinovaginal bulbs
- the sinovaginal bulbs proliferate to form a solid vaginal plate
- proliferation continues at the cranial end of the plate, increasing the distance between the uterus and urogenital sinus
- by month 5, the vaginal outgrowth is completely canalised
Why might duplications of the uterus arise?
- duplications of the uterus result from a lack of fusion of the paramesonephric ducts in a local area or throughout their normal line of fusion
- the most severe form is uterus didelphys (double uterus)
- the least severe form is uterus arcuatus in which there is a slight indentation in the centre
- uterus bicornis is relatively common and involves the uterus having 2 horns but entering a common vagina
What can happe if there is complete or partial atresia of one of the paramesonephric ducts?
- the rudimentary part lies as an appendage to the well-developed side
- the lumen does not communicate with the vagina, so complications are common
- if atresia involves both sides, atresia of the cervix may result
What are the 3 main causes of abnormalities of the uterus and what are they associated with?
- failure of paramesonephric ducts to fuse
- failure of uterine septum to degenerate
- failure of one paramesopnephric duct to elongate
- uterine abnormalities are associated with higher rates of miscarriage, premature delivery or dystocia (difficult birth)
Who is affected by persistent Müllerian duct syndrome?
Why does this occur?
- it affects genetic males and involves a mutation in the AMH gene
- there is no AMH production, so the paramesonephric ducts persist
- both mesonephric and paramesonephric derivatives develop
- there is normal male external genitalia, but it is associated with cryptochidism
What is hypospadias and why does it occur?
What is the main symptom and how can it be repaired?
- fusion of the urethral folds is incomplete, resulting in abnormal openings along the inferior aspect of the penis
- abnormal openings are usually near the glans, along the shaft or near the base of the penis
- it causes difficulty urinating and can be repaired surgically using the foreskin
What is epispadias and why does it occur?
What other abnormality is this associated with?
- this occurs when the urethral meatus is located on the dorsal surface of the penis
- it can occur in isolation but is often associated with exstrophy of the bladder and abnormal closure of the ventral body wall
- it results from improper location of the genital tubercle posterior to the urogenital sinus
- this results in the urethral groove being located on the dorsal surface of the penis
