13. Reproductive System (TT) Flashcards
What are the different endocrine steps that must be fulfilled in each parent in order for successful transmission of fertile gametes and for the maintenance of pregnancy?
- Correct chromosomal complement (chromosomal sex)
- Functional testis or ovary containing germ cells (gonadal sex)
- Possess the correct internal and external anatomical male and female genitalia (phenotypic sex)
- Demonstrate appropriate sexual behaviour patterns (behavioural sex)
In other words, in order for a fertile adult to develop, they must have the karyotype of one of the sexes, functioning gonads and correct internal and external genitalia. There may be problems with the development of any of these that cause failure of normal sexual development.
How many chromosomes do humans typically have? How many of these are sex chromosomes?
46 chromosomes -> 22 pairs of autosomes and 2 sex chromosomes
What are autosomes and how many do humans have?
Non-sex chromosomes -> Humans have 22 pairs.
What is chromosomal genotype of the sex chromosomes for males and females?
- Males = XY
- Females = XX
Describe when the sex of a human is determined and how.
- It is determined at conception
- This is when the sperm introduces either another X or a Y into the egg, making the genotype XX or XY respectively
What are gonads?
- The organs that produce the gametes
- i.e. Testes or ovaries
How does the presence of a Y chromosome affect the gonads?
It causes the somatic cells of the gonads to develop into testes rather than ovaries.
What can be said about the genes of the Y chromosome?
- Most of the genes on it are unique to this chromosome
- There are around 20 genes benefiting males on this chromosome -> 10 of these are specific to the testes
What is an X-linked inheritance?
A pattern of inheritance for a genetic condition that occurs when a copy of a gene located on the X chromosome has a genetic variant.
Which chromosome determines sex and what is the evidence for this?
- The Y chromosome actively determines maleness
- Evidence for this came from two syndromes:
- Turner’s syndrome = XO genotype -> Results in an infertile female
- Klinefelter’s syndrome = XXY genotype -> Results in an infertile male
What is Klinefelter’s syndrome and what are the symptoms?
- It is characterised by the genotype XXY
- Symptoms:
- Infertility
- Small testes
What is Turner’s syndrome and what are the symptoms?
- It is characterised by the genotype XO
- Symptoms:
- Do not produce eggs
Describe how the Y chromosome leads to male development. [IMPORTANT]
- On the Y chromosome, there is a segment called the SRY gene (sex-determining region of the Y chromosome)
- It encodes a single sex-determining transcription factor (SRY protein) that controls signalling leading to male development
- It does this because the SRY protein controls downstream gene expression that triggers a cascade of events -> First, the development of the testes, which release molecules that lead to male internal genitalia differentiation and male external genitalia, along with other male characteristics
Draw the cascade by which SRY leads to differentiation of the entire male reproductive system. [IMPORTANT]
What does TDF stand for and what is it?
- Testes-developing factor
- It is another name for the SRY protein that determines testes development
What does SRY stand for?
Sex-determining region Y
What is the evidence for the importance of SRY is determining maleness?
- Humans with one Y chromosome and multiple X chromosomes are usually male -> Due to the presence of the SRY gene
- XX males (XX male syndrome, infertile) -> In this SRY gene is translocated to one of X chromosomes
- XY females -> This occurs due to the lack of, or mutation in SRY
Is the whole Y chromosome required for development of the male sex? What is the experimental evidence for this?
- Only the SRY region is required
- Experiments in mice show that introduction of the SRY region alone into XX mice is sufficient to give rise to male testes, internal genitalia and external genitalia
- However, these are not completely male because other genes on the Y chromosome are required for different characteristics -> For example, sperm cannot survive in the XX environment, making these mice infertile
What is the ‘default’ sex?
- The need for SRY to produce testes and male genitalia suggests that females are the ‘default’ sex
- However, the presence of two copies of the DAX-1 gene in an XY organism, can cause reversal to the female sex -> It has been suggested that DAX-1 acts as an ‘anti-testes’ factor
What are the different parts of the reproductive system that must form in development?
- Gonads
- Internal genitalia
- External genitalia
Does the presence of an XX or XY karyotype necessarily mean that ovaries or testes will form?
No, there may be problems in their development.
What are the main stages of the development of the gonads?
- Formation of a gonadal ridge
- Migration of primordial germ cells
- Differentiation of the undifferentiated gonad into either the testes or ovaries
Describe in detail the process of gonad development. [IMPORTANT]
- Intermediate mesoderm gives rise to not only the nephric structures, but also a gonadal ridge on the medial aspect near the mesonephric region (in 5th week) -> This is induced by WT1, SF1 and LHX9, and it also involves the migration of primordial germ cells from the yolk sac via the hindgut
- There is continued migration of these primordial germ cells, and in the 6th week somatic support cells from the coelomic epithelium invest these cells and associate with them. Structures known as sex cords are formed by the support cells.
- Now the processes diverge for males and females.
In males:
- The sex cords proliferate by mitosis to give the testis cords (made of somatic support cells), which contain the germ cells trapped inside. The presence of SRY induces somatic support cells around the germ cells to form Sertoli cells. The primordial germ cells inside are now called the prospermatogonia.
- The primordial cells concentrate in the medulla and the cortex regresses.
- The testis cordis become canalised at puberty and differentiate into seminiferous tubules (site of the germination, maturation, and transportation of the sperm cells within the male testes).
- The Sertoli cells organise into the rete testis (network of delicate tubules that carries sperm from the seminiferous tubules to the efferent ducts)
- Leydig cells form and can secrete testosterone from the 8th week.
In females:
- The sex cords dissociate. The absence of SRY means that the somatic support cells instead differentiate into primitive follicle cells that envelope the germ cells, so that the primordial germ cells are in nests. These will become the primordial follicles. Meiosis commences but then arrests in the foetus. Primordial follicles start to develop but undergo apoptosis until puberty.
- The primordial follicles concentrate in the cortex and the medulla regresses.
- Oogonia proliferate.
The gonads then descend with the help of the gubernaculum, which is a ligamentous structure.
What part of which germ layer do the gonads form from?
Intermediate mesoderm (just like the kidneys and adrenals)
When does the formation of the gonads begin?
In the 5th week
The formation of what structure begins the formation of the gonads? Where does this occur?
- Gonadal ridge (a.k.a. genital ridge)
- It forms on the medial aspect of the intermediate mesoderm in the region of the mesonephros
Draw a diagram to show the position of the gonadal ridge relative to the kidneys and other structures.
What happens if the gonadal ridge fails to develop?
It results in no gonad formation.
What are some genes that induce the formation of the gonadal ridge? What is the clinical relevance of each?
- WT1 (Wilms Tumour) -> When disrupted it causes kidney tumours in children. When knocked out, it causes failure of kidney and gonad formation.
- SF1 (Steroidogenic factor) -> When knocked out, it causes failure of kidney and gonad development
- LHX9 -> When knocked out, it causes failure of gonad development.
The migration of the primordial germ cells to the urogenital ridge is important in allowing the gonadal ridge to form.
What are primordial germ cells and what is their importance?
- Germ cells that are in the process of migrating to the gonads
- They are important in the formation of the gonadal ridge and the gonads
What is the source of primordial germ cells and how do they migrate? What happens to them when they arrive? [IMPORTANT]
- Develop in epiblast
- Migrate to the gonadal ridge via the yolk sac and hind gut
- When they arrive, somatic support cells from the coelomic epithelium surround these cells and associate with them
What are two genes that are important in primordial germ cells reaching the gonads? [EXTRA]
- Steel
- BMPs
What happens to the somatic support cells that associate with the germ cells in the developing gonads?
- In males, they become the Sertoli cells
- In females, they become the granulosa cells (follicle cells)
What is the interaction of WT1, SF1 and LHX9 with SRY (sex-determining region Y protein)?
- WT1, SF1 and LHX9 are involved in the development of the gonads
- These genes act UPSTREAM of SRY, so when there are knockouts or mutations in these that cause failure of the gonads to develop, then the lack of gonads will mean that phenotypical development that follows will be female
After the gonadal ridge forms, what happens to it?
It descends and thickens gradually between the 5th and 7th week.
When does the sexual differentiation of genetic males begin?
In 6th week, with the SRY expression.
When the undifferentiated gonad differentiates into the testes, what histological structures are formed? Where are the germ cells found?
- Seminiferous tubules, which contain within their walls:
- Germ cells
- Sertolli cells -> Support and nourish the developing spermatagonia
- Interstitial tissue:
- Leydig cells -> Produce testosterone
- Blood
- Lymph vessels
When the undifferentiated gonad differentiates into the ovary, where are the developing follicles found?
In the cortex of the ovary stromal tissue. {Don’t worry, this is covered later)
Describe how differentiation of the undifferentiated gonad into the testes or ovaries occurs. [IMPORTANT]
It is mostly caused by SRY, but other genes help with this.
Testes:
- Presence of SRY or SOX9 -> SRY leads to differentiation of the mesoderm to form Sertoli cells and products of these cells direct testis tubule and interstitial cell formation
Ovaries:
- Occurs in the absence of SRY or SOX9 -> Sertoli cells do not develop and the equivalent mesodermal cells will become the granulosa cells which surround the oocytes
- Absence of WNT4 in XX (mouse, human) causes partial masculinisation (testis-like gonad; no male ext genitalia)
- DAX1 duplication in XY humans causes sex reversal -> DAX1 suppresses testis
What structures are formed when primordial germ cells migrate into the gonadal ridge and associate with the somatic support cells?
Sex cords (made of the somatic support cells, with the germ cells inside the cords)
Describe what happens to sex cords in males.
- The sex cords proliferate by mitosis to give the testis cords (made of somatic support cells), which contain the germ cells trapped inside. The presence of SRY induces somatic support cells around the germ cells to form Sertoli cells. The primordial germ cells inside are now called the prospermatogonia.
- The primordial cells concentrate in the medulla and the cortex regresses.
- The testis cordis become canalised at puberty and differentiate into seminiferous tubules (site of the germination, maturation, and transportation of the sperm cells within the male testes).
- The Sertoli cells organise into the rete testis (network of delicate tubules that carries sperm from the seminiferous tubules to the efferent ducts)
- Located between the testis cordis, Leydig cells form and can secrete testosterone from the 8th week.
Describe what happens to sex cords in females.
- The sex cords dissociate. The absence of SRY means that the somatic support cells instead differentiate into primitive follicle cells that envelope the germ cells, so that the primordial germ cells are in nests. These will become the primordial follicles. Meiosis commences but then arrests in the foetus. Primordial follicles start to develop but undergo apoptosis until puberty.
- The primordial follicles concentrate in the cortex and the medulla regresses.
- Oogonia proliferate.
Compare the names for the differentiated forms of the primordial germ cells in males and females.
- Males -> Spermatogonia
- Females -> Oocytes
Compare the cells that derive from stromal cells in the gonads in males and females.
- In males -> Leydig cells
- In females -> Thecal cells
What is the gubernaculum and what is its function?
It is a ligamentous structure made of mesenchyme that tethers the caudal ends of the gonads and helps with their descent.
Describe the migration of gonads in males and females.
Males:
- As the body of the fetus grows, the testes become more caudal.
- They pass through the inguinal canal around the 28th week, and reach the scrotum by the 33rd week.
- The gubernaculum helps with this and the scrotal ligament is the adult remnant of this.
Females:
- The ovaries initially migrate caudally in a similar fashion to the testes from their origin on the posterior abdominal wall.
- However they do not travel as far, reaching their final position just within the true pelvis.
- The gubernaculum also helps withthe descent and becomes the ovarian ligament and round ligament of the uterus.
What genes are important in the descent of the testis and what is the name for the failure of this to happen?
- Testosterone and DHT, Mullerian Inhibiting Factor, and members of the HOX gene family are involved in testicular descent into scrotum
- Mutations of any of these results in abnormal testicular descent (prevalence 5.5% of boys at term)
- This is called crytpoorchidism [EXTRA]
What is the importance of the Leydig cells in male reproductive development?
They secrete testosterone, which induces the formation of the correct internal reproductive structures.
What are the internal genitalia?
- All of the reproductive organs within the true pelvis
- In females -> Ovaries, uterine (fallopian) tubes, uterus, cervix and vagina
- In males -> Testis, epididymis, vas deferens and accessory glands
What are the two important ducts involved in the development of the internal genitalia?
- Mesonephric duct (Wolffian duct)
- Paramesonephric duct (Mullerian duct)
Describe the development of the internal genitalia in males and females.
- A paramesonephric duct (Mullerian duct) forms alongside the mesonephric duct (Wolffian duct) in the indifferent stage of internal genitalia development -> This formation is induced by the Wnt4 signalling molecule
- In females, the paramesonephric duct (Mullerian duct) is retained -> It becomes the uterine tubes, uterus and upper part of the vagina. The mesonephric duct degenerates.
- In males, the mesonephric duct (Wolffian duct) is retained -> It becomes the epididymis, vas deferens and seminal vesicles. The paramesonephric duct degenerates. The prostate forms from the urogenital sinus.
- The differentiation into male internal genitalia from the ‘default’ female is caused by two important signalling molecules:
- Testosterone (produced by testicular Leydig cells) -> Causes maintenance of the mesonephric (Wolffian) duct.
- Mullerian inhibiting factor (a.k.a. anti-Mullerian hormone) (also produced by the testicular Sertoli cells) -> Causes atrophy of the paramesonephric (Mullerian) duct
Which of the mesonephric and paramesonephric ducts is retained in males and females?
- Males -> Mesonephric (Wolffian) duct
- Females -> Paramesonephric (Mullerian) duct
What signalling molecule is important in the formation of the paramesonephric duct?
Wnt4
What structures does the paramesonephric duct form in females?
Uterine tubes, uterus and upper part of the vagina.
What structures does the mesonephric duct form in males?
Epididymis, vas deferens and seminal vesicles.
What does the prostate form from in males?
Urogenital sinus
What is the role of the testes in differentiation of the internal genitalia?
They produce:
- Testosterone -> Causes retention of the Wolffian duct and differentiation into the male internal genitalia
- Mullerian inhibiting factor (a.k.a. anti-Mullerian hormone) -> Causes atrophy of the Mullerian duct
In essence, this is a step of the differentiation cascade that results from SRY.
What is the main androgen involved in male sexual differentiation?
Testosterone
Testosterone and Mullerian inhibiting factor are involved in the differentiation of the male testes. Where is each produced?
- Testosterone -> Leydig cells of the testis
- MIF -> Sertoli cells of the testis
In what sex do the mesonephric tubules form a reproductive structure?
- Males
- Differentiate to vas efferentia
Where do the mesonephric and paramesonephric ducts end?
At the cloaca.
Describe the formation of the external genitalia in males and females.
- Up to the 8th week, the external genitalia are undifferentiated:
- There is a genital tubercle and genital swelling
- The genital tubercle becomes the phallus in the undifferentiated state
- Female differentiation occurs when an ovary or no gonads are present, while male differentiation occurs when testis are present (Leydig cells produce testosterone)
- In males:
- The phallus becomes the glans of the penis and urethral groove forms on the ventral surface of the phallus -> Fusion of the urogenital folds surrounding the urethral groove along the ventral surface of the penis.
- The genital swelling becomes the scrotum -> There is a midline closure of the labioscrotal folds, which forms the scrotum.
- These changes occur due to dihydrotestosterone (which is a converted form of the testosterone from the testis)
- In females:
- The phallus becomes the clitoris
- Genital swelling becomes the labia majora (do not fuse like in males)
- Urethral folds instead form the labia minora
- Urogenital groove remains open, forming the vestibule where the vagina and urethra open
Describe the structure of the undifferentiated external genitalia.
Up to the 8th week, the external genitalia are undifferentiated:
- There is a genital tubercle and genital swelling
- The genital tubercle becomes the phallus in the undifferentiated state
What causes the undifferentiated external genitalia to differentiate?
- In males -> Dihydrotestosterone (converted form of testosterone from the Leydig cells of the testis)
- In females -> Lack of dihydrotestosterone + Presence of oestrogen
Describe the differentiation of the structures in the undifferentiated external genitalia in males.
- Genital tubercle -> Phallus -> Glans of penis
- Genital swelling -> Scrotum
- Fusion of the urogenital folds surrounding the urethral groove on the ventral side of the penis
This is drives by dihydrotestosterone (DHT).
Describe the differentiation of the structures in the undifferentiated external genitalia in females.
- Genital tubercle -> Phallus -> Clitoris
- Genital swelling -> Labia majora
- Genital folds -> Labia minora
- Urethral groove remains open due to no fusion of the folds, so this is where the vagina and urethra open.
This is due to the lack of dihydrotestosterone and the presence of oestrogen.
How is dihydrotestosterone produced and where?
- It is produced from testosterone
- Catalysed by 5α-reductase
- Occurs in Leydig cells in the testis
What hormone is responsible for the formation of the prostate?
Dihydrotestosterone (DHT)
What are the 3 main hormones that cascade from SRY?
- Testosterone
- Dihydrotestosterone
- Mullerian inhibiting factor
What are the roles of testosterone, dihydrotestosterone and Mullerian inhibiting factor in male sexual differentiation?
- Testosterone -> Internal genitalia (acts on the mesonephric duct)
- Dihydrotestosterone -> External genitalia + Prostate
- MIF -> Atrophy of the Mullerian duct
What is the vestigial remainder of the Mullerian duct in males? [EXTRA]
Appendix testis -> Torsion is when these twist around themselves, cutting off their own blood supply.
What is the vestigial remainder of the Wolffian duct in females? [EXTRA]
- There may be clusters of epididymal ducts remaining
- Remanants may form cysts, risking torsion
What is adrenal hyperplasia and how can it affect individuals?
- It is when the adrenal glands produce too much androgens (e.g. testosterone)
- Congenitally is usually occurs because of defects that mean that aldosterone and cortisol are produced less, and the intermediates enter testosterone synthesis instead
- In females, this can leads to masculinisation
- In males, this can lead to precocious puberty
Draw a summary of all of male and female reproductive system development and sexual differentiation.
What are the parts of the male reproductive system that you need to know about?
- Testis in scrotum
- Seminiferous tubules
- Vasa efferentia
- Epididymis
- Vas deferens
- Seminal vesicles
- Prostate gland
- Penis
Draw a diagram of the male reproductive system.
What are the three parts of the urethra? Describe the change in direction along the urethra.
- Prostatic
- Membranous (through the perineal membrane)
- Penile (spongy)
There is a 90 degree change in direction between the membraneous and penile section.
Describe the pathway of spermatozoa from the testis.
- Seminiferous tubules in testis
- Epididymis (storage)
- Ductus (vas) deferens
- Ductus deferens combines with secretions from the seminal vesicles at the ejaculatory duct
- Urethra in the prostate gland
- Rest of urethra
What do the testes produce?
- Spermatazoa
- Testosterone
How is the prostate gland involved in the reproduction?
- Secretes about 30% of seminal fluid.
- The urethra runs through it.
Draw the structure of the testis and epididymis.
Describe the parts of the testis and their functions.
- Seminiferous tubules -> Site of spermatazoa production
- Tunica albuginea -> Contains the seminiferous tubules
- Rete testis -> Drain the seminiferous tubules
- Epididymis -> Drains the rete testis
- Tunica vaginalis -> Double-layered serous membrane that covers the testes
- Vasa efferentia -> Connect the rete testis to the epididymis
Where in the testis are spermatozoa produced?
Seminiferous tubules
What are the parts of the epididymis?
From superior to inferior:
- Head
- Body
- Tail
These become increasingly straight.
Where are spermatozoa stored?
In the epididymis.
What are the vasa efferentia?
The ducts that connect the rete testis to the epididymis.
Describe the path of spermatazoa out of the testis and into the vas deferens.
- Seminiferous tubules
- Rete testis
- Vasa efferentia
- Epididymis
- Vas deferens
According to the spec, where does the vas deferens pass?
Through the inguinal canal.
Describe the descent of the testis in development and how this relates to the inguinal canal.
- Testis develop on the posterior abdominal wall
- When they descend and pass obliquely through the muscle layers of the anterior abdominal wall, forming the inguinal canal
- It is guided by the gubernaculum
- It involves the testes pushing out the transversalis fascia, transversus abdominus, internal oblique and external oblique muscles into the scrotum (although the transversus abdominus are not incorporated into the scrotum)
What is the name for the outpouching of the peritoneum into the future scrotum during testis descent? What usually happens to it?
- Processus vaginalis
- It is usually obliterated before birth, using just the tunica vaginalis
What are the layers of the scrotum? What is each derived from?
From inner to outer:
- Internal spermatic fascia -> From transversalis fascia
- Cremasteric fascia and muscle -> From internal oblique
- External spermatic dascia -> From external oblique
Then around only the testis is the dartos muscle and fascia, plus the subcutaneous skin.
What are the two important muscles in the scrotum and what is their function?
- Cremaster
- Dartos
They work together in regulating the temperature of the testes and protection by drawing them into the body.
What is the innervation of the cremaster muscle?
Innervated by the genital branch of the genitofemoral nerve (L1/L2).
What type of nerve fibres is the dartos muscle innervated by?
Sympathetic
What is the dartos fascia?
It divides the scrotum into the left and right sections.
Describe the blood supply and drainage of the testis and epididymis. [IMPORTANT]
Blood supply:
- Each testis and epididmyis is supplied by a testicular artery, which is a branch of the aorta
Blood drainage:
- Each testis is drained by vesicular veins are arranged in a pampiniform venous plexus
- These pass through the inguinal canal that unite to form a single vein
- Left testicular vein -> Drains into left renal vein
- Right testicular vein -> Drains directly into IVC
Describe the lymphatic drainage of the testis.
Lymphatic vessels run alongside the arteries and drain into para-aortic lymph nodes.
Where can pain in the testis be referred to?
Area of the abdominal wall supplied by the nerve root T10.
What is the cremasteric reflex?
Describe the pathway of the ductus (vas) deferens.
- Ascend from tail of epididymis
- Join spermatic cord
- Pass through the inguinal canal
- Enter pelvic cavity via the deep inguinal ring
- Pass over external iliac vessels
- Pass medial to the ureters
- Finally join with the ampulla of the ductus deferens
- This then joins with the outflow of the seminal vesicles to form the ejaculatory duct
What are the ejaculatory ducts?
- Each ejaculatory duct is formed by the union of the vas deferens with the duct of the seminal vesicle.
- They pass through the prostate, and open into the urethra.
Which side of the bladder do the vas deferens pass on?
Posterior
Draw the position of the vas deferens in relation to the bladder and surrounding structures.
What is the function of the seminal vesicles?
- They secrete alkaline secretions that form a large component of seminal fluid.
- It contains fructose, which acts as a fuel.
- It also coagulates the sperm together.
How does passage of fluid along the vas deferens, seminal vesicles and ejaculatory ducts occur?
There is muscle in the walls of the ducts and they are heavily innervates for contraction.
Describe the blood supply of the ductus (vas) deferens, bladder and prostate.
Arterial supply (all derived from internal iliac artery):
- Ductus deferens -> Umbilical artery
- Bladder and prostate -> Superior and inferior vesicular arteries
Venous drainage:
- Prostate -> Drains back to vertebral venous plexus
What are the different openings into the prostatic urethra?
- Prostatic utricle -> Not functional
- Openings of ejaculatory ducts
- Openings of prostatic ducts
Describe the different lobes of the prostate gland.
Describe the lymphatic drainage of the male reproductive system.
Where does the male superificial perineal membrane lie?
It lies superficial to the perineal membrane. It is where the penis is found.
Describe the structure of erectile tissues of the penis.
- 2 corpus cavernosa
- These run along the penis and then diverge to form the crura (sing. crus)
- Corpus spongiosum
- Runs between and inferior to the corpus cavernosa.
- At the base, it is enlarged to give the bulb of the penis.
- At the tip it is enlarged to give the glans of the penis.
- Urethra runs through the corpus spongiosum
What is the penis anchored to?
Perineal membrane and ischial ramus
Which chamber of the penis ends in the glans?
Corpus spongiosum
Which chamber of the penis contains the urethra?
Corpus spongiosum
Describe the different muscles that assist the functioning of the penis.
- Bulbospongiosus -> Compresses the bulb of the penis and the corpus spongiosum, helping with the emptying of the urethra. Also assists in maintaining penile erection by preventing venous outflow.
- Ischiocavernosus -> Force blood from the crura into the distal parts of the corpus cavernosum and preventing venous outflow, helping with erection.
- Superficial transverse perineal muscle -> Assist with maintaining the position of the perineal body.
Describe the innervation of the muscles that assist the functioning of the penis (bulbospongiosus and ischiocavernosus).
Pudendal nerve (S2-S4)
What surrounds the chambers of the penis?
Fascial sheath
What is the margin of the glans of the penis?
Corona of the glans
What is another name for the foreskin?
Prepuce
Describe the arterial blood supply and drainage of the penis.
Pudendal artery branches into:
- Dorsal artery -> Supplies dorsal surface of penis
- Deep artery -> Supplies corpus cavernosum
Superficial and deep dorsal veins drain the penis.
Which nervous system is responsible for erection?
Parasympathetic
Describe how erection occurs.
- Normally, the helicine arteries of the corpora are contracted, so that little blood flows into the penis
- Parasympathetic contribution to erection:
- When achieving erection, the helicine arteries of corpora relax
- Cavernous nerves (S2-S4)
- Somatic contribution to erection:
- Contraction of bulbospongiosus and ischiocavernosus impedes venous return
- Pudendal nerve
Which nervous system is responsible for emission of semen (not ejaculation!)?
Sympathetic
Which nervous system is responsible for ejaculation of semen?
Somatic
Describe how emission and ejaculation occurs.
Sympathetic nervous system controls emission:
- Sympathetic fibres initiate contraction of smooth muscle of epididymal ducts, ductus deferens, seminal vesicles and prostate in sequence
- Sperm, seminal and prostatic secretions enter prostatic urethra and penile bulb
- Sympathetic stimulation (L1-L2) of internal urethral sphincter prevents ejaculation into bladder
Somatic nervous system controls ejaculation:
- Rhythmic contraction of bulbospongiosus (pudendal nerve S2-S4) moves semen along spongy urethra resulting in ejaculation
Draw a schematic summary of the male pelvic floor and perineum.
How does sexual reproduction generate genetic diversity?
- By mixing the genes from both parents
- Parents vary in their genetic constitution
- Gonads produce haploid germ cells, gametes, by meiosis
- Gonads produce sex hormones which direct pre- & post-natal development.
What is the purpose of sexual behaviour?
To bring together the gametes to produce a new individual.
What is the male reproductive strategy and what is the result of this?
- Males mate opportunistically, from puberty to old age in humans
- The testis must be able to produce very large numbers of active spermatozoa almost continuously
- This requires continuous division of stem cells
What is a gamete?
A mature haploid male or female germ cell which is able to unite with another of the opposite sex in sexual reproduction to form a zygote.
What is the male gamete?
Spermatazoon (pl. spermatazoa)
How long does mature spermatazoon production take and what is the result of this?
- 60 days
- This means that different parts of the testes contain spermatazoa at different stages of development
Describe the structure of a spermatazoon.
- Smallest human cells -> Diameter at head is only 3µm
- Highly condensed DNA in the head
Draw the structure of the testis.
In what structures of the testis are spermatazoa matured?
Seminiferous tubules
Describe the histological structure of seminiferous tubules.
- Surrounded by basal lamina and a layer of contractile myoid cells
- Within the tubules, the Sertoli cells extend from the basement membrane to the tubule lumen -> Junctional complexes between their lateral cell membranes divide the tubule into a basal and a luminal compartment.
- Between the Sertoli cells are the spermatagonia cells derived from primordial germ cells -> Situated in the basal compartment.
- Later stages of spermatazoa development may be found further towards the lumen.
From what part and what cells of the seminiferous tubules are spermatazoa produced?
- The spermatagonia cells of the epithelial layer
- These are derived from primordial germ cells
What are Sertoli cells derived from?
Mesenchyme of the gonadal ridge
What is the function of the Sertoli cells?
Two main functions:
- They have a supportive and nutrient function in the development of spermatazoa from spermatagonia.
- Form the blood-testis barrier
What is found between seminiferous tubules?
The interstitium, containing:
- Leydig cells -> Play an important role in hormone production
- Blood
- Nerves
- Lymph vessels
What is shown on this diagram?
- The arrows on the left point to the seminiferous tubules, containing Sertoli cells and developing spermatazoa
- The arrow on the right points to the interstitial space, containing Leydig cells
Note: The lumens of the seminiferous tubules look different to each other because different sections of the tubules are at different stages of development.
Describe the process of spermatogenesis.
- In the foetus, mitosis of primordial germ cells populates the testis with spermatogonia (on the sides of the seminiferous tubules)
- These are quiescent until puberty
- Spermatogonia A cells divide my mitosis to give spermatogonia B and reform the spermatagonia pool
- Spermatogonia B form primary spermatocytes by mitosis
- Primary spermatocytes go through meiosis I and II to produce secondary spermatocytes and then round spermatids
- They retain cytosplamic bridges between the cells during this whole process to allow for transfer of mRNA and proteins of haploid cells
- Round spermatids differentiate to form spermatozoa, which involves losing much of the cytoplasms
What do the labels and arrow on this diagram show?
- The arrow points to the basal lamina and myoid cells
- SC = Sertoli cells
- ES = Early spermatid
- LS = Late spermatid
What is shown by the arrows on this image?
Blood-testis barrier
Recap briefly how meiosis occurs in spermatogenesis.
- After DNA replication in the diploid stem germ cell (spermatogonium), there is pairing and recombination.
- Then primary spermatocyte goes through two cell divisions required to produce the haploid gametes.
- Each diploid cell that enters meiosis therefore produces four haploid cells.
- Cell divisions are incomplete, so there are still cytoplasmic bridges and also junctional contacts with surrounding Sertoli cells.
Compare how DNA packing in spermatozoa is different to somatic cells.
- In somatic cells:
- Packed on histones
- This is the “beads on a string” model
- In sperm
- Packed on protamines
- This takes the form of a ring structure -> “Annulus”
The packing in sperm is much tighter.
Describe the changes in the proteins that associate with the DNA during spermatogenesis.
Draw a diagram to show the different phases of spermatogenesis.
Note: The shaded cells show the development of a single cell.
Describe the ‘wave’ of spermatogenesis.
- Looking along a single seminiferous tubule, it can be seen that different parts of the tubule are at different stages of spermatogenesis.
- As a result, there are always mature spermatozoa available in the tubule
- The mechanism for this co-ordination likely involves signalling along the gap junctions of the Sertoli cells
At what phase of spermatogenesis are these samples?
- Top left = Maturation phase
- Top right = Grouping phase
- Bottom left = Release phase (since almost no spermatazoa present)
Describe how germ cells are able to pass through the tight junctions of Sertoli cells. [EXTRA?]
- Only α-mannosidase IIx is able to produce complex carbohydrate-containing oligosaccharide chains that terminate in GlcNAc (square) and fucose (diamond), rather than mannose (circle) or galactose (not shown).
- It is this unique oligosaccharide that germ cells use to adhere to Sertoli cells.
- This allows them to slowly and gradually pass between the Sertoli cells without damaging them.
Describe how spermiogenesis (maturation of spermatids into spermatazoa) occurs.
- Golgi phase:
- Golgi becomes localised assymetrically on one side of the cell
- Proximal and distal centrioles assemble on the opposite side to the Golgi + Flagellum begins to form
- Cap phase:
- Nuclear pores of the nucleus migrate caudally towards the side facing the flagellum
- Mitochondria migrate towards the flagellum
- Acrosome begins to form on the cranial side of the cell
- Acrosome phase:
- Acrosome enlarges
- Mitochondria begin to surround the mid-part of the flagellum in a spiral pattern
- Large part of cytoplasm is lost as cytoplasmic droplet
- Acrosomal phase
- Acrosome
Draw the structure of a spermatazoon.
Describe the hormonal control of testis, including feedback. [IMPORTANT]
- Hypothalamus produces kisspeptin, which stimulates production of GnRH (gondotrophin release hormone)
- This stimulates the release of LH and FSH
- LH acts on Leydig cells, stimulating androgen production (especially testosterone) -> This leads to development of secondary sex characteristics and stimulates Sertoli cells
- FSH acts on Sertoli cells -> This leads to activation of spermatogenesis and the production of inhibin
- Myoid cells allow cross-talk between different reproductive cells
- Androgens and inhibin carry out negative feedback by inhibiting the hypothalamus and the actions of the pituitary
How does feedback occur in the control of testis function?
- Androgens (e.g. testosterone) and inhibin feedback negatively on the hypothalamus and pituitary
- This means that concentrations of FSH and LH are kept constant
Describe and draw the histology of the epididymis.
- Each epididymis is formed by a single convoluted tubule seen in multiple cross sections.
- Lined by a tall pseudostratified columnar epithelium.
- These cells have stereocilia on their luminal surface and tight junctions between their lateral membranes (creating the blood-epididymis barrier).
What is the histological structure and function of the vas deferens?
- Transports spermatozoa and can store them in its ampulla
- Contracts mainly in relation to sympathetic (NA and ATP) stimulation -> Important in ejaculation
What is the histological structure and function of the seminal vesicles?
Structure:
- Lobulated tubulo-saccular glands.
- Their pseuostratified columnar epithelium forms many branched processes which extend into the lumen of the saccules
- Each saccule is surrounded by smooth muscle innervated by sympathetic nerves
Function:
- Produce the major fluid component of semen upon ejaculation
- Produce the fructose that provides energy for sperm motility
- Affect signalling from uterine lining to conceptus
- Contracts mainly in relation to sympathetic (NA and ATP) stimulation -> Allowing emission
What is the histological structure and function of the prostate gland?
Structure:
- Epithelium varies from columnar to cuboidal
- The fibromuscular stroma is extensive and surrounds the glandular acini.
- Number of lobes made up of tubulo-alveolar glands -> Surrounded by large amounts of fibromuscular connective tissue. During emission, the prostatic secretions are forced by the smooth muscle of the stroma (sympathetic innervation).
Function:
- Produces about 25% of the ejaculate, containing:
- Proteolytic enzymes (fibrinolysin)
- Zinc
- acid phosphatase
- Transferrin
- Prostate-specific antigen (PSA) which is used in the detection of prostate cancer.
- Plays a role in the capacitance of sperm (changes spermatozoa must undergo in order to have the ability to penetrate and fertilise an egg)
What are the constituents of semen and where do they come from?
How does the counter-current heat exchange work in the testis?
- Blood entering the scrotum passes through a blood vessel system of intermingled vessels -> This cools the blood down
- The blood exiting the scrotum is heated back up by the descending blood
- This counter-current system helps to keep the testis cool
Draw a diagram of the female reproductive system.
Label this.
Describe the relative positions of the bladder, uterus and rectum in the pelvis.
What are the 4 parts of the Fallopian (uterine) tubes?
- Fimbriae
- Infundibulum
- Ampulla
- Isthmus
What are the 3 parts of the cervix?
From superior to inferior:
- Internal os (top narrowing)
- Cervical canal
- External os (bottom narrowing)
What are the fornices of the vagina?
- The fornices are superior recesses of the vagina formed by the protrusion of the cervix into the vaginal vault.
- There is a large posterior fornix and a smaller anterior fornix with two small lateral fornices.
Label this.
Draw the view that would be seen during a cervical exam.
What two important terms describe the alignment of the uterus (relative to the vagina)?
- Anteflexed -> Body of cervix is bent so as to form a slight n shape
- Anteverted -> Cervix is bent forward relative to the axis of the vagina
What is the broad ligament?
- A double-fold of peritoneum
- It extends from the sides of the uterus medially to the pelvic sidewalls laterally and the pelvic floor inferiorly
What are the different parts of the broad ligament and what does each cover?
- Mesometrium -> Uterus
- Mesosalpinx -> Fallopian tubes
- Mesovarium -> Ovaries
Label this. (Posterior view)
Draw a schematic diagram of the female pelvic floor and perineum.
Label this laparoscopic picture of the female pelvis.
Draw a diagram showing the blood supply to the female reproductive system.
Describe and explain the innervation of the female reproductive tract.
- The pelvic pain line divides the female reproductive tract, passing just above the cervix
- Above this line:
- All the structures (uterus, Fallopian tubes and ovaries) are covered by parietal peritoneum (they are intraperitoneal)
- Innervated by sympathetic and visceral afferent nerves (T12-L2)
- Below this line:
- All of the structures (cervix and vagina) are subperitoneal (not covered by the parietal peritoneum)
- Pelvic splanchnics S2-S4 (parasympathetic) provide most of the innervation
- Pudendal nerves S2-S4 (parasympathetic) provide the innervation to the distal vagina and perineum
What nerves innervate above the pelvic pain line?
Sympathetic + Visceral afferents (T12-L2)
What is the perineum divided into?
- Superficial perineal pouch -> Between the perineal membrane and superficial fascia
- Deep perineal pouch -> Between the perineal membrane and the pelvic floor muscles
Label this drawing of the vagina.
What ducts are found at the lower side of the vagina?
The ducts of the greater vestibular gland (Bartholin gland)
Label this.
Label this. (Note that the overlying muscles have been removed)
Label this.
It is the deep perineal pouch in females.
Describe the blood supply to the penis and scrotum.
- The supply to the penis comes from the internal pudendal artery (a branch of the internal iliac artery):
- Artery of bulb -> Supplies the bulb of the penis
- Deep artery of penis -> Supplies corpus cavernosum
- Dorsal artery of penis -> Supplies distal corpus spongiosum and facial skin of penis
- (The internal pudendal artery also gives rise to the posterior scrotal artery that supplies some of the scrotum)
- The supply to the scrotum comes from the external pudendal artery (a branch of the femoral artery):
- Anterior scrotal artery -> Supplies most of the scrotum
Draw the path of the internal pudendal artery and pudendal nerve below the pelvic floor. [EXTRA?]
Draw a graph to show how the number of germ cells in a female changes over time.
Describe the structure of an ovary.
Outer cortex:
- Contains follicles
- Follicles contain the oocytes
- Different follicles can be observed at different stages of development
- Between follicles there is the stroma which contains corpora lutea and corpora albicantia -> These are derived from previously ovulated follices and those in the process of regressing (atresia)
Inner medulla:
- Contains blood vessels, nerves and steroid-secreting cells
Describe the process of oogenesis.
- Before birth, the oogonia divide by mitosis
- The primary oocyte is arrested in prophase I before birth
- It then builds up RNA and protein, and rests until puberty
- After puberty, in each menstrual cycle, cohorts of oocytes mature by completing meiosis I
- Meiosis I yields a polar body (that dies) and a secondary oocyte
- Secondary oocyte is arrested in meiosis II
- Meiosis II is arrested after fertilisation, yielding a second polar body (that dies) and a zygote
Draw how oogenesis occurs alongside follicle development.
Draw a primordial follicle, secondary follicle and tertiary follicle.
Label this ovarian follicle.
Label this ovarian follicle, including what the arrows point to/show.
- The black arrow shows where the zona granulosa is
- The white arrows point to black carbon deposits, which are created by injecting carbon into the blood. This shows that this is the theca layer, which is the only layer to receive blood supply.
Draw a diagram to show which parts of follicle development are dependent on gonadotrophins.
Describe how the hypothalamo-pituitary-gonadal (HPG) axis works.
- The neurohormone kisspeptin controls the release of gonadotrophin-releasing hormone (GnRH) from the hypothalamus
- GnRH acts on the pituitary to promote release of FSH and LH, which act on the ovaries
- The ovaries feedback to the hypothalamus and pituitary via the hormones progesterone, estrogen and inhibin
Describe the effects of LH and FSH on the ovaries. [IMPORTANT]
- LH acts at LH receptors on theca interna cells
- Stimulates the production of androgens via cAMP (the androgen is called androstenedione)
- FSH acts at FSH receptors on granulosa cells to produce aromatase
- Aromatase converts androgens to estradiol
- FSH also stimulates the production of inhibin
Describe how and why the concentrations of these hormones change during the follicular phase of the menstrual cycle:
- FSH
- LH
- Estradiol
- Progesterone
- Inhibin
[IMPORTANT]
- FSH gradually rises at first, causing follicular development to happen
- A gradual rise in inhibin causes inhibition of the HPG axis and therefore inhbits the production of FSH, so FSH levels drop -> This leads to selection of just one pre-ovulatory follicle (since FSH prevents follicular atresia)
- This dominant follicle releases estradiol, which is stimulatory of the HPG axis (NOTE: After ovulation it is inhibitory) so it leads to a surge of LH (and FSH)
- The LH surge leads to ovulation
- Progesterone is very low throughout
Describe how the LH surge before ovulation occurs and why it is important.
- Rising estradiol sensitises the pituitary to GnRH (NOTE: It is inhibitory after ovultion!)
- The surge of LH acts on LH receptors on granulosa cells of the dominant follicle to cause ovulation and complete the first meiotic division
Describe how the LH surge causes ovulation.
- Granulosa cells at first have only FSH receptors, but in follicles selected to ovulate, FSH induces the expression of LH receptors on mural granulosa cells.
- LH binds to LH receptors, which increases cAMP
- cAMP acts to stimulate:
- Prostagladins
- This stimulates vascular permeability, which increases intrafollicular pressure and provides a driving force for extrusion of oocyte
- Formation of plasmin from plasminogen
- This stimulates collagenase and also breaks down collagen, which weakens the follicle wall
- This leads to ovulation
- Prostagladins
Label this diagram of the ovary.
Describe how and why the concentrations of these hormones change during the luteal phase of the menstrual cycle:
- FSH
- LH
- Estradiol
- Progesterone
- Inhibin
[IMPORTANT]
- LH surge at ovulation induces change in the steroidogenic enzymes produced by the follicle (which is now the corpus luteum)
- This leads to increased progesterone and estrogen (estradiol) production for about 7 days (stimulated by slow LH pulses) -> Inhibin spikes too
- FSH and LH also fall shortly after ovulation due to inhbition of the HPG axis by progesterone and estradiol
- Luteolysis (breakdown of the corpus luteum) will occur causing progesterone and estrogen concentrations to fall
Describe the uterus wall changes during the menstrual cycle. What hormones are involved in each phase? [IMPORTANT]
Proliferative phase (before ovulation):
- Estrogen controls this phase
- Thickening of the endometrium
- Glands become more coiled and densely-packed
- Cells develop cilia and villi
Secretory phase (after ovulation):
- Progesterone
- Endometrium thickens to its maximum thickness
- Glands become enven more coiled and have a saw-toothed appearance
- If no fertilisation occurs, no HcG is present so corpus luteum dies, so no progesterone is produced:
- Spiral arteries that supply the uterus constrict
- This causes the endometrium to degenerate
Draw how the vasculature of the uterus lining changes during the menstrual cycle.
How is puberty started?
- We are not sure, but it is likely due to kisspeptin activating the GnRH pulse generator.
- The thing that triggers kisspeptin is likely to be body weight, with leptin as the likely signal.
What causes the symptoms of menopause?
Menopause is when all of the ovarian follicles are depleted. The failure of follicular development means that ovarian secretion of estrogens and inhibins is drastically reduced This causes:
- Lack of negative feedback at the pituitary and excessive secretion of LH and FSH
- Lack of oestrogen action on a variety of tissues including bone, skin, hair, liver, cause osteoporosis, thinned skin and hair, and an unwanted rise in plasma cholesterol and attendant increase in cardiovascular disease.
How do stress and lactation affect the menstrual cycle?
Stress and lactation inhibit ovulation -> This is to prevent pregnancy during stressful times (conservation of resources) or just after having a baby.
Summarise the hormonal changes, follicular changes and uterine changes during the menstrual cycle.
