13. Reproductive System (TT) Flashcards
(355 cards)
1
Q
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?
A
- 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.
2
Q
How many chromosomes do humans typically have? How many of these are sex chromosomes?
A
46 chromosomes -> 22 pairs of autosomes and 2 sex chromosomes
3
Q
What are autosomes and how many do humans have?
A
Non-sex chromosomes -> Humans have 22 pairs.
4
Q
What is chromosomal genotype of the sex chromosomes for males and females?
A
- Males = XY
- Females = XX
5
Q
Describe when the sex of a human is determined and how.
A
- 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
6
Q
What are gonads?
A
- The organs that produce the gametes
- i.e. Testes or ovaries
7
Q
How does the presence of a Y chromosome affect the gonads?
A
It causes the somatic cells of the gonads to develop into testes rather than ovaries.
8
Q
What can be said about the genes of the Y chromosome?
A
- 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
9
Q
What is an X-linked inheritance?
A
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.
10
Q
Which chromosome determines sex and what is the evidence for this?
A
- 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
11
Q
What is Klinefelter’s syndrome and what are the symptoms?
A
- It is characterised by the genotype XXY
- Symptoms:
- Infertility
- Small testes
12
Q
What is Turner’s syndrome and what are the symptoms?
A
- It is characterised by the genotype XO
- Symptoms:
- Do not produce eggs
13
Q
Describe how the Y chromosome leads to male development. [IMPORTANT]
A
- 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
14
Q
Draw the cascade by which SRY leads to differentiation of the entire male reproductive system. [IMPORTANT]
A
15
Q
What does TDF stand for and what is it?
A
- Testes-developing factor
- It is another name for the SRY protein that determines testes development
16
Q
What does SRY stand for?
A
Sex-determining region Y
17
Q
What is the evidence for the importance of SRY is determining maleness?
A
- 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
18
Q
Is the whole Y chromosome required for development of the male sex? What is the experimental evidence for this?
A
- 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
19
Q
What is the ‘default’ sex?
A
- 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
20
Q
What are the different parts of the reproductive system that must form in development?
A
- Gonads
- Internal genitalia
- External genitalia
21
Q
Does the presence of an XX or XY karyotype necessarily mean that ovaries or testes will form?
A
No, there may be problems in their development.
22
Q
What are the main stages of the development of the gonads?
A
- Formation of a gonadal ridge
- Migration of primordial germ cells
- Differentiation of the undifferentiated gonad into either the testes or ovaries
23
Q
Describe in detail the process of gonad development. [IMPORTANT]
A
- 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.
24
Q
What part of which germ layer do the gonads form from?
A
Intermediate mesoderm (just like the kidneys and adrenals)
25
When does the formation of the gonads begin?
In the 5th week
26
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
27
Draw a diagram to show the position of the gonadal ridge relative to the kidneys and other structures.
28
What happens if the gonadal ridge fails to develop?
It results in no gonad formation.
29
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.
30
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
31
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
32
What are two genes that are important in primordial germ cells reaching the gonads? [EXTRA]
* Steel
* BMPs
33
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)
34
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
35
After the gonadal ridge forms, what happens to it?
It descends and thickens gradually between the 5th and 7th week.
36
When does the sexual differentiation of genetic males begin?
In 6th week, with the SRY expression.
37
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
38
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)
39
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
40
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)
41
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.
42
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.
43
Compare the names for the differentiated forms of the primordial germ cells in males and females.
* Males -\> Spermatogonia
* Females -\> Oocytes
44
Compare the cells that derive from stromal cells in the gonads in males and females.
* In males -\> Leydig cells
* In females -\> Thecal cells
45
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.
46
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.
47
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]
48
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.
49
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
50
What are the two important ducts involved in the development of the internal genitalia?
* Mesonephric duct (Wolffian duct)
* Paramesonephric duct (Mullerian duct)
51
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
52
Which of the mesonephric and paramesonephric ducts is retained in males and females?
* Males -\> Mesonephric (Wolffian) duct
* Females -\> Paramesonephric (Mullerian) duct
53
What signalling molecule is important in the formation of the paramesonephric duct?
Wnt4
54
What structures does the paramesonephric duct form in females?
Uterine tubes, uterus and upper part of the vagina.
55
What structures does the mesonephric duct form in males?
Epididymis, vas deferens and seminal vesicles.
56
What does the prostate form from in males?
Urogenital sinus
57
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.
58
What is the main androgen involved in male sexual differentiation?
Testosterone
59
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
60
In what sex do the mesonephric tubules form a reproductive structure?
* Males
* Differentiate to vas efferentia
61
Where do the mesonephric and paramesonephric ducts end?
At the cloaca.
62
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
63
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
64
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
65
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).
66
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.
67
How is dihydrotestosterone produced and where?
* It is produced from testosterone
* Catalysed by 5α-reductase
* Occurs in Leydig cells in the testis
68
What hormone is responsible for the formation of the prostate?
Dihydrotestosterone (DHT)
69
What are the 3 main hormones that cascade from SRY?
* Testosterone
* Dihydrotestosterone
* Mullerian inhibiting factor
70
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
71
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.
72
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
73
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
74
Draw a summary of all of male and female reproductive system development and sexual differentiation.
75
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
76
Draw a diagram of the male reproductive system.
77
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.
78
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
79
What do the testes produce?
* Spermatazoa
* Testosterone
80
How is the prostate gland involved in the reproduction?
* Secretes about 30% of seminal fluid.
* The urethra runs through it.
81
Draw the structure of the testis and epididymis.
82
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
83
Where in the testis are spermatozoa produced?
Seminiferous tubules
84
What are the parts of the epididymis?
From superior to inferior:
* Head
* Body
* Tail
These become increasingly straight.
85
Where are spermatozoa stored?
In the epididymis.
86
What are the vasa efferentia?
The ducts that connect the rete testis to the epididymis.
87
Describe the path of spermatazoa out of the testis and into the vas deferens.
* Seminiferous tubules
* Rete testis
* Vasa efferentia
* Epididymis
* Vas deferens
88
According to the spec, where does the vas deferens pass?
Through the inguinal canal.
89
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)
90
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
91
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.
92
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.
93
What is the innervation of the cremaster muscle?
Innervated by the genital branch of the genitofemoral nerve (L1/L2).
94
What type of nerve fibres is the dartos muscle innervated by?
Sympathetic
95
What is the dartos fascia?
It divides the scrotum into the left and right sections.
96
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**
97
Describe the lymphatic drainage of the testis.
Lymphatic vessels run alongside the arteries and drain into para-aortic lymph nodes.
98
Where can pain in the testis be referred to?
Area of the abdominal wall supplied by the nerve root T10.
99
What is the cremasteric reflex?
100
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
101
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.
102
Which side of the bladder do the vas deferens pass on?
Posterior
103
Draw the position of the vas deferens in relation to the bladder and surrounding structures.
104
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.
105
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.
106
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
107
What are the different openings into the prostatic urethra?
* Prostatic utricle -\> Not functional
* Openings of ejaculatory ducts
* Openings of prostatic ducts
108
Describe the different lobes of the prostate gland.
109
Describe the lymphatic drainage of the male reproductive system.
110
Where does the male superificial perineal membrane lie?
It lies superficial to the perineal membrane. It is where the penis is found.
111
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
112
What is the penis anchored to?
Perineal membrane and ischial ramus
113
Which chamber of the penis ends in the glans?
Corpus spongiosum
114
Which chamber of the penis contains the urethra?
Corpus spongiosum
115
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.
116
Describe the innervation of the muscles that assist the functioning of the penis (bulbospongiosus and ischiocavernosus).
Pudendal nerve (S2-S4)
117
What surrounds the chambers of the penis?
Fascial sheath
118
What is the margin of the glans of the penis?
Corona of the glans
119
What is another name for the foreskin?
Prepuce
120
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.
121
Which nervous system is responsible for erection?
Parasympathetic
122
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
123
Which nervous system is responsible for emission of semen (not ejaculation!)?
Sympathetic
124
Which nervous system is responsible for ejaculation of semen?
Somatic
125
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
126
Draw a schematic summary of the male pelvic floor and perineum.
127
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.
128
What is the purpose of sexual behaviour?
To bring together the gametes to produce a new individual.
129
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
130
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.
131
What is the male gamete?
Spermatazoon (pl. spermatazoa)
132
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
133
Describe the structure of a spermatazoon.
* Smallest human cells -\> Diameter at head is only 3µm
* Highly condensed DNA in the head
134
Draw the structure of the testis.
135
In what structures of the testis are spermatazoa matured?
Seminiferous tubules
136
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.
137
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
138
What are Sertoli cells derived from?
Mesenchyme of the gonadal ridge
139
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
140
What is found between seminiferous tubules?
The interstitium, containing:
* Leydig cells -\> Play an important role in hormone production
* Blood
* Nerves
* Lymph vessels
141
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.
142
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
143
Is there any meiosis in the male foetus?
No (unlike in the female) -\> The primordial germ cells populate the testis with spermatogonia by mitosis.
144
Does spermatogenesis produce more than 1 fertile spermatozoon?
Yes, all of the spermatozoa produced are fertile.
145
Summarise spermatogenesis, including the types of cell division that occur.
* Spermatogonium A
* (Mitosis)
* Spermatogonia B (one goes back to replenish spermatogonia pool)
* (Mitosis)
* Primary spermatocytes
* (Meiosis I)
* Secondary spermatocytes
* (Meiosis II)
* Round spermatids
* (Differentiation)
* Spermatozoa
146
How many spermatozoa can be produced from one spermatogonium and why?
* 8
* This is because there are 4 divisions, but after the first division one of the spermatagonia B cycles back to replenish the spermatogonia pool.
147
Describe the movement as a spermatagonium matures to form a spermatazoon.
The cells move gradually towards the lumen as they mature.
148
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
149
What is the blood-testis barrier, how does it form and what is its purpose?
* It is the barrier that is formed by the tight junctions between the Sertoli cells
* This divides the seminiferous tubules into a basal compartment and adluminal compartment
* This is useful because spermatogenesis only begins long after birth, so sperm components would appear foreign to the blood and launch an immune response. Therefore, the blood-testis barrier allows the adluminal contents to be separated from the blood and controlled.
150
At what point in spermatogenesis do the products cross the blood-testis barrier?
Primary (early) spermatocytes go from the basolateral to the adluminal compartment just as meiosis begins.
151
What is shown by the arrows on this image?
Blood-testis barrier
152
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.
153
What is spermiogenesis?
The differentiation of spermatids to give spermatozoa.
Note: This is not the same as spermatogenesis.
154
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.
155
Describe the changes in the proteins that associate with the DNA during spermatogenesis.
156
How often do new cohorts of spermatazoa begin to develop? Cells from how many cohorts are present at any one point?
* New cohort every 12 days
* At any given time, cells from 4 different cohorts are present (since development takes 60 days)
157
What does the stage of spermatogenesis refer to? What are the 4 different stages?
* It refers to the combination of the 4 different points in the development of spermatazoa that may be seen at a given point in the seminiferous tubule
* The 4 stages are named after the phase that the most developed spermatazoa are at:
* Maturation
* Release
* Elongation
* Grouping
158
Draw a diagram to show the different phases of spermatogenesis.
Note: The shaded cells show the development of a single cell.
159
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
160
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)
161
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.
162
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
163
What are some structural and functional features that a spermatazoon must have?
* Have haploid complement of DNA, protected against damage
* Be motile -\> Flagellum
* Have receptors for zona pellucida & oocyte
* Be able to penetrate the cumulus oophorus & zona pellucida
* Be capable of activating an oocyte
164
Draw the structure of a spermatazoon.
165
Where are the oocyte receptors and acrosome on a spermatazoon?
* Acrosome -\> At the tip of the head
* Oocyte receptor -\> At the base of the head
166
Describe how spermatogenesis is activated at puberty.
* Hypothalamic **kisspeptin** neurons become activated (partly due to body fat-lean ratio)
* Kisspeptin activates pulsatile secretion of **GnRH** (gonadotrophin release hormone) from GnRH neurons (starts at night)
* Hypothalamic GnRH stimulates secretion of gonadotrophins **FSH** (follicle-stimulating hormone) and **LH** (luteinising hormone) from the pituitary
Summary: Kisspeptin from hypothalamus -\> GnRH from hypothalamus -\> FSH and LH from pituitary
167
What are the two important hormones in control of testis function?
* FSH - Follicle stimulating hormone
* LH - Luteinising hormone
168
What are the effects of FSH and LH on the testis?
* FSH -\> Initially stimulates Sertoli cell division, then secretion, which initiates and maintains spermatogenesis
* LH -\> Acts on the Leydig cells to produce testosterone
169
Is testosterone the most active form of testosterone?
No, dihydrotestosterone is, which is made by 5-alpha reductase.
170
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
171
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
172
What is ABP and how is it involved in spermatogenesis?
* Androgen binding protein
* Its production in Sertoli cells is stimulated by FSH
* ABP binds to testosterone, accumulating it in Sertoli cells, which stimulates proper development of the spermatozoa
173
What is the evidence that LH, FSH and GnRH play a role in testis function?
Knockout mice:
* Hypogonadal
* No GnRH is produced
* Maturation of seminiferous tubules is defective and no mature sperm is produced
* LH receptor knockout
* No sperm can be produced
* FSH or FSH receptor knockout
* Several phases of sperm maturation occur, so FSH is not absolutely required for spermatogenesis
174
Which hormone leads to the development of secondary sexual characteristics at puberty?
Testosterone
175
Describe the developmental abnormalities in:
* Hypogonadal organism
* LH receptor knockout
* FSH receptor knockout
* Hypogonadal organism (no GnRH) and LH receptor knockout -\> Reproductive tract is virtually non-existent
* FSH receptor knockout -\> Reproductive tract is still mostly present, but testes are smaller
176
How long does it take for sperm to pass through the epididymis?
4-6 weeks
177
What is the importance of the epididymis to sperm?
Without maturation in the epididymis, sperm cannot fertilise.
178
What are some of the androgen-dependent functions of the epididymis relating to sperm?
* Removes cytoplasmic droplet from spermatozoa
* Adds a glycoprotein coat over sperm head - prevents premature activation of acrosome
* Concentrates spermatozoa and can maintain in storage
* Allow development of unidirectional motility
179
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).
180
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
181
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
182
On what hormone are the functions of the epididymis, seminal vesicles and prostate dependent on?
Testosterone
183
What sort of epithelium lines the epididymis, vas deferens and seminal vesicles?
Pseudostratified columnar epithelium
184
What are the accessory glands in the reprouctive system?
* Seminal vesicles
* Prostate
* Bulbourethral gland
185
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)
186
What are the constituents of semen and where do they come from?
187
Describe the different parts of male sexual intercourse, including the events that occur during each and how they are under nervous control.
* Arousal
* **Erection**
* Due to **parasympathetic** control -\> Not typically cholinergic, but NO leading to increased cGMP
* Causes arteriolar vasodilation
* Elevation of scrotum
* Elevation and swelling of testes
* Plateau
* Distension of penis and testes
* Mucous bulbourethral gland secretions
* Due to **parasympathetic** control
* Orgasm
* **Emission**
* Contraction of vas deferens, seminal vesicles, prostate and relaxation of urethral sphincter
* Due to **sympathetic** control -\> Noradrenaline
* **Ejaculation**
* Rhythmic contraction of perineal striated muscle (bulbospongiosus) and anal sphincter
* Due to **somatic** control –\> Pudendal nerve
* Refractory
* Resolution (return to non-aroused state)
188
Which nerve and muscles control ejaculation?
* Bulbospongiosus muscle and anal sphincter
* Controlled by the pudendal nerve (somatic)
189
How does viagra work?
* Sildenafil (Viagra) is a potent competitive inhibitor of PDE5 (phosphodiesterase type 5 inhibitor) which is responsible for degradation of cGMP in the corpus cavernosum
* This inhibition leads to increases in cGMP, which causes arteries in the corpora cavernosa to dilate, causing lots of blood to flow into the penis
* The PDE5 enzyme is found primarily in the penis – therefore ‘specific’.
* The drug stays in the bloodstream for about four hours, until removal by the liver and kidneys.
190
What is priapism and what are the different types?
An erection that lasts more thatn 6 hours:
* Ischaemic -\> Low flow, veno-occlusion
* Non-ischaemic -\> High flow, arterial
These are important distinctions because they require different treatments.
191
What are some important processes that contribute to the control of testis temperature?
* Descent of the testis (in development)
* Control of testis position in adult life
* Counter-current heat exchange
192
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
193
Draw a diagram of the female reproductive system.
194
What are the ovaries covered by and what is this continuous with?
* Cuboidal epithelium
* Continuous with the peritoneum
195
What is a Graffian follicle?
A fluid-filled structure in the mammalian ovary within which an ovum develops prior to ovulation.
196
Into what cavity is an ovum released when a Graffian follicle ruptures (at ovulation)? Where does it go?
* Into the peritoneal cavity
* This is because the epithelial covering of the ovaries is continuous with the peritoneum
* The ovum is collected by the motile uterine tube
197
What are the Fallopian tubes and what is their function?
* They transport the ova from the ovary to the uterus each month
* They are usually the site of fertilisation
198
What is another name for the Fallopian tubes?
Uterine tubes
199
What is the infundibulum and what is its function?
It is the end of the Fallopian tube that cups the ovary and collects the ovum that is released.
200
Where does fertilisation usually take place?
In the Fallopian tubes.
201
What type of structure is the uterus?
Thick muscular
202
Which compartments is the uterus continuous with and through with structures?
* Peritoneal cavity via the Fallopian tubes
* Perineum via the vagina
203
What is the endometrium and what is its function?
* The lining of the uterus
* It is prepared monthly for the possible reception of a fertilised ovum
204
What structure is the vagina continuous with and at what point?
Uterus, at the uterine cervix.
205
What is the cervix?
The lower, narrow part of the uterus that joins to the top of the vagina.
206
What is the distal opening of the vagina called?
Vaginal orifice (introitus)
207
Describe how the different structures in the female reproductive tract are continuous with each other.
The ovaries are cupped by the infundibulum of the Fallopian tubes, which connect to the uterus, the cervix of which joins to the vagina.
208
Which female reproductive structures are intraperitoneal, subperitoneal and perineal?
Intraperitoneal:
* Ovaries
* Fallopian tubes
Subperitoneal:
* Uterus
* Vagina
Perineal:
* Vagina
209
What is the pouch of peritoneum that is anterior to the uterus?
Vesicouterine pouch
210
What is the pouch of peritoneum that is posterior to the uterus?
Rectouterine pouch (of Douglas)
211
Label this.
212
Describe the relative positions of the bladder, uterus and rectum in the pelvis.
213
Does the peritoneal cavity extend into the pelvis?
Yes, but it does not reach the pelvic floor. It lies on top of most of the pelvic organs, except the ovaries and Fallopian tubes, which are intraperitoneal.
214
What are the 4 parts of the Fallopian (uterine) tubes?
* Fimbriae
* Infundibulum
* Ampulla
* Isthmus
215
What are fimbriae and what is their function?
* The finger-like projections located at the ends of the fallopian tubes, closest to the ovaries.
* The majority of the fimbriae do not touch the ovary but rather hover very close by, activated by hormones to catch a released egg and move it down into the fallopian tube.
216
In what cavity is the uterus?
Entirely in the pelvic cavity, unless in pregnancy when it can extend into the abdomen.
217
At what point do the Fallopian tubes join to the uterus?
Lateral cornu (horns) of the uterus
218
What are the 3 main parts of the uterus that the spec mentions?
* Fundus (top of the uterus)
* Body
* Cervix
219
What is the top of the uterus called?
Fundus
220
What is the cervix?
It is the narrowing at the bottom of the uterus, where the uterus joins to the vagina.
221
What are the 3 parts of the cervix?
From superior to inferior:
* Internal os (top narrowing)
* Cervical canal
* External os (bottom narrowing)
222
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.
223
Which direction does the vagina extend from the cervix?
Inferiorly and anteriorly
224
Label this.
225
Draw the view that would be seen during a cervical exam.
226
What is the name for the gap through which the ovum passes into the ampulla of the Fallopian tube?
Ostium of the Fallopian tube
227
Describe the position of the uterus relative to the bladder.
It is posterior and superior.
228
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
229
What main factors may change the alignment of the uterus?
* Bladder filling
* Childbirth
* Pathology
230
What is mobile retroversion of the uterus?
When the uterus becomes retroverted rather than anteverted, as a result of the bladder filling.
231
What pathologies can retroversion of the uterus signal?
* Pelvic adhesions / infection
* Endometriosis
* Pelvic tumour
232
What are the four important ligaments relating to the uterus?
* Broad ligament (not strictly a ligament)
* Round ligament of uterus
* Ligament of ovary
* Suspensory ligament of the ovary
233
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
234
What are the different parts of the broad ligament and what does each cover?
* Mesometrium -\> Uterus
* Mesosalpinx -\> Fallopian tubes
* Mesovarium -\> Ovaries
235
Which ligament contains the ovarian blood vessels?
Suspensory ligament of the ovary
236
What ligament tethers the ovaries to the uterus?
Ligament of ovary
237
What is the remanent of the gubernaculum in females?
* Round ligament of the uterus
* It is the female counter-part of the spermatic cord, and it runs through the inguinal canal
238
Label this. (Posterior view)
239
Draw a schematic diagram of the female pelvic floor and perineum.
240
How is the position of the ovaries described in the spec?
Intraperitoneal, on the posterior aspect of the broad ligament.
241
What is the importance of the pelvic floor in females?
The muscles prevent prolapse of the pelvic structures, including the uterus and cervix.
242
Label this laparoscopic picture of the female pelvis.
243
What are the 3 main arteries supplying the female reproductive system? What do these branch from?
* Uterine artery -\> From abdominal aorta
* Ovarian artery -\> From internal iliac artery
* Vaginal artery -\> From internal iliac artery or ovarian artery
244
Describe the blood supply and drainage of the ovaries. [IMPORTANT]
Supply:
* **Ovarian artery** -\> From the **abdominal aorta**
Drainage:
* Drains to the **IVC**
245
Describe the blood supply and drainage of the uterus. [IMPORTANT]
Supply:
* **Uterine artery** from the **internal iliac artery**
Drainage:
* **Internal iliac vein**
246
Describe the blood supply to the vaginal.
Vaginal artery, which is a branch of the internal iliac artery or uterine artery.
247
Draw a diagram showing the blood supply to the female reproductive system.
248
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
249
Remember to add some flashcards on the innervation of the male reproductive system.
Do it.
250
What is a good way to remember pelvic innervation?
* If something is innervated by parasympathetic fibres, it is very likely to be innervated by the S2-S4 level, especially the pudendal nerve
* If something is innervated by sympathetic fibres, it is likely to be from the thoracic and lumbar regions, since this is where sympathetic fibres come from
251
What nerves innervate above the pelvic pain line?
Sympathetic + Visceral afferents (T12-L2)
252
What nerves innervate below the pelvic pain line?
* Pelvic splanchnics S2-S4 (parasympathetic) provide most of the innervation
* Pudendal nerves S2-S4 (parasympathetic) provide the innervation to the distal vagina and perineum
253
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
254
What are the muscles lying just above the perineal membrane in females (in the deep perineal pouch) and what is their function?
* Compressor urethrae + External urethral sphincter
* They are involved in continence
255
What are the muscles lying just below the perineal membrane in females (in the superficial perineal pouch) and what is their function?
* Ischiocavernosus + Bulbospongiosus
* They are involved in the erectile process (e.g. of the clitoris)
256
Label this drawing of the vagina.
257
What ducts are found at the lower side of the vagina?
The ducts of the greater vestibular gland (Bartholin gland)
258
What are two important erectile muscles in females? Where are they found? What is the innervation of these?
* Bulbospongiosus
* Ischiocavernosus
They are found in the superficial perineal pouch, just inferior to the perineal membrane. They are innervated by S2-S4 pudendal nerve.
259
Label this.
260
Label this. (Note that the overlying muscles have been removed)
261
Label this.
It is the deep perineal pouch in females.
262
What are the deep perineal pouches continuous with?
Ischioanal fossae (posteriorly).
263
What does the erectile tissue in females consist of?
1. Crura of the clitoris and the body of the clitoris
2. Bulbs of the vestibule
These are erected by the ischiocavernosus and bulbospongiosus muscles.
264
Where are the Bartholin (greater vestibular) glands and what is their function?
* In the superficial perineal space, associated with the bulbs of the vestibule
* They produce mucus that acts as lubrication for the vagina
265
What is the clinical relevance of the ureter and surrounding arteries?
* The ureter passes below uterine artery
* This means there is a risk of damage to the ureter when the artery is ligated during surgery
266
What does the internal pudendal artery supply and what is its path?
* It supplies the perineum and external genitalia
* It is a branch of the internal iliac artery
* Exits the pelvis via the greater sciatic foramen and enters the perineum via the lesser sciatic foramen, passing through the pudendal canal
267
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
268
Describe how the internal pudendal artery enters the perineum.
Via the pudendal canal (ischioanal fossa).
269
Draw the path of the internal pudendal artery and pudendal nerve below the pelvic floor. [EXTRA?]
270
What are the two functions of the ovaries?
* Production of gametes
* Production of sex hormones
271
Describe the general development and change in number of germ cells in a woman over her lifetime.
* The pool of stem cells (oogonia) increases by mitosis before birth (just as in males)
* Meiosis starts and then arrests during fetal life.
* After that, no more oocytes are formed.
* From then on, partial development then atresia (apoptosis) of follicles (containing oocytes) continually depletes the ovary of oocytes in the later part of fetal and throughout reproductive postnatal life.
* Of the 6-7 million primary oocytes produced, only about 400 will be ovulated.
272
What is the name for the stem cells in a woman during the fetal stage that go on to give oocytes?
Oogonia
273
In what phase is the development of oocytes arrested in females at birth?
Prophase I of meiosis
274
How many primary oocytes are produced and how many of those will go on to be ovulated?
* 6-7 million are produced
* Only 400-500 are ovulated
275
Draw a graph to show how the number of germ cells in a female changes over time.
276
What are follicles in the ovary?
* A fluid-filled sac that contains an immature egg, or oocyte.
* During ovulation, a mature egg is released from a follicle.
277
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
278
Describe the blood supply and drainage of the ovaries.
Each ovary receives an ovarian artery from the aorta and drains into a pampiniform plexus of veins.
279
Is the blood flow to the ovaries constant?
No, it varies cyclically.
280
How is each ovary held in place?
* Each ovary is attached to the posterior aspect of the broad ligament by the mesovarium (through which vessels/nerves enter).
* Ova therefore pass briefly into the peritoneal cavity before entering the uterine (Fallopian) tube.
281
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
282
Draw how oogenesis occurs alongside follicle development.
283
What is the earliest stage of ovarian follicle development called?
Primordial follicle
284
What are the different stages of ovarian follicle development?
* Primordial follicle
* Primary follicle
* Secondary follicle
* Tertiary follicle
285
What are the different layers of cells in an ovarian follicle?
The number of these layers depends on the stage of development:
* Oocyte with surrounding zona pellucida
* Granulosa cells with basal lamina around them
* Theca cells
286
Draw a primordial follicle, secondary follicle and tertiary follicle.
287
Label this ovarian follicle.
288
What happens to the granulosa cells during follicle development?
They go from flat to more cuboidal. The number of their layers also increases.
289
What marks the change from primordial follicle to primary follicle to secondary follicle to tertiary follicle?
* Primordial follicle -\> When there is only one layer of thin granulosa cells around the oocyte
* Primary follicle -\> When there is only layer of more rounded granulosa cells around the oocyte
* Secondary follicle -\> When there are two layers of granulosa cells around the oocyte
* Tertiary follicle -\> When there are multiple layers of granulosa cells around the oocyte, with perhaps an antrum
290
How does the zona pellucida form?
It is secreted by the oocyte.
291
What are the different layers of theca cells in the ovarian follicle and what does each do?
* Theca interna -\> Secretes steroids (just like Leydig cells)
* Theca externa -\> Forms capsule
292
What is the function of the granulosa cells?
Production of steroids and LH receptors.
293
Describe ovarian follicle development.
* First there are primordial follicles -\> Consist of a primary oocyte surrounded by a single layer of flat pregranulosa cells.
* Primary follicle forms when the primary oocyte enlarges and the granulosa cells become rounded -\> FIGα, a germ-cell transcription factor is essential
* Thereafter a few follicles start the development process every few days. Most are destined for atresia.
* Mitosis in the single layer of granulosa cells (to give two layers) and differentiation of surrounding stromal cells to form thecal cells -\> Produces a secondary follicle
* The granulosa cells, stimulated by FSH now secrete fluid which coalesces to form an antrum and the follicle is called an early antral (tertiary) follicle.
* Growth continues to produce a preovulatory Graffian follicle -\> The large antrum separates mural granulosa cells lining the basal lamina of the follicle wall from cumulus granulosa cells (the corona radiata) which surround the oocyte.
294
What is the equivalent of granulosa cells and theca cells in the male?
* Granulosa cells = Sertoli cells
* Theca cells = Leydig cells
295
What receptors do granulosa and theca cells have?
* Granulosa -\> FSH
* Theca -\> LH
296
How many antral follicles are produced per menstrual cycle?
Around 10, of which usually 1 goes on to become the dominant Graffian follicle.
297
What are the 4 stages of ovarian follicle development mentioned in the spec?
* Primordial
* Antral
* Pre-ovulatory
* Atretic
298
What determines which of the follicles in the ovary develop further and which undergo atresia?
It is dependent on FSH action.
299
Describe the blood supply to an ovarian follicle.
The blood supply to the developing follicle is restricted to the thecal layer.
300
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.
301
What are some important molecules for the formation and development of ovarian follicles?
* Formation -\> FIGα is a transcription factor
* Development -\> GDF-9 is an ovary-specific glycoprotein
302
In what stage of follicle development does the theca layer appear?
When it is a secondary follicle.
303
At what point in follicle development does further development become dependent on FSH?
Once the follicle is a mature secondary follicle.
304
What is the difference between an antral follicle and pre-ovulatory follicle?
* An antral follicle is one in which a small antrum has formed
* A pre-ovulatory follicle is one in which the antrum has grown to almost entirely surround the oocyte, so it is ready for ovulation -\> Usually there is only one of these
305
Draw a diagram to show which parts of follicle development are dependent on gonadotrophins.
306
What is ovarian follicle rescue?
This is the way in which FSH prevents follicles from undergoing atresia. [CHECK THIS]
307
What is the idea of selection of ovarian follicles?
It is the way in which only one ovarian follicle is selected as the dominant follicle that goes on to become the pre-ovulatory follicle.
308
What controls the action of the ovaries?
Hypothalamo-pituitary axis
309
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**
310
What are the two hormones that control the action of the ovaries?
The two major gonadotrophin hormones are named after their function in females:
* Follicle-stimulating hormone (FSH)
* Luteinising hormone (LH)
Estrogen also has local effects within the ovary.
311
Describe the structure of FSH and LH, and summarise their function.
* Both are glycoproteins comprising a hormone-specific β chain and an α chain common to LH, FSH and TSH.
* Coordinated action of FSH and LH is responsible for follicle maturation and ovulation.
312
Where do GnRH neurons originate from developmentally? What is the result of this?
They develop in the nose before migrating to the brain. This has been implicated in the way in which pheromones can influence human reproduction.
313
In what pattern does the body release GnRH?
It is released in a pulsatile manner, every 60 to 240 minutes.
314
What is Kallman's syndrome and how can it be treated?
* A condition causing anosmia associated with hypogonadism in which the GnRH-releasing neurons that develop in the nose never reach the brain.
* It can be treated by administering GnRH every 60 to 240 minutes.
315
What activates the gonads at puberty?
Kisspeptin activates the pulsatile release of GnRH from the hypothalamus.
316
Which hormones are required for ovarian follicle development?
* FSH
* LH
317
What are the targets of FSH and LH within the ovaries?
* FSH -\> Granulosa cells
* LH -\> Theca interna cells
318
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
319
How long is the menstrual cycle?
28 days
320
What are the two phases of the menstrual cycle?
* Follicular phase
* Luteal phase
321
On which day does each menstrual cycle start?
On the first day of menstruation.
322
Explain the difference between the follicular and luteal phase of the menstrual cycle.
* Follicular phase -\> When the reproductive system is dominated by products of one developing follicle.
* Luteal phase -\> After ovulation, when the products of the corpus luteum dominate.
323
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
324
Around what day in the menstrual cycle does ovulation happen?
Day 14
325
What is estradiol?
It is the strongest of the three estrogens and it is produced by the dominant follicular hormone.
326
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
327
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
328
After ovulation, what do the remaining granulosa and theca interna cells of the dominant follicle form?
Corpus luteum
329
Label this diagram of the ovary.
330
Describe the changes in vasculature of the corpus luteum. Why does this happen?
* Blood vessels invade the corpus luteum through the basal lamina.
* This is due to the LH surge that triggers ovulation.
331
Summarise the effects of the LH surge during the menstrual cycle.
It causes:
* The oocyte to enter the 2nd meiotic division, extruding one polar body
* Release of the oocyte and its cumulus of granulosa cells by inducing degenerative changes in the follicle wall
* In-growth of blood vessels into the corpus luteum
* Corpus luteum to secrete progesterone, with some estradiol.
332
What is luteinization?
The formation of the corpus luteum after ovulation.
333
What happens to the corpus luteum?
The corpus luteum grows for about 7 days then, if pregnancy does not supervene, degenerates, and a new cycle starts.
334
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
335
What produces progesterone and what are its effects?
* It is produced by the corpus luteum (so it is only secreted for about 7 days after ovulation)
* It inhibits the HPG axis, so production of LH and FSH is inhibited
336
What does luteolysis result in and why?
* As the corpus luteum dies, there is lower production of progesterone, estradiol and inhibin
* Therefore, negative feedback on the HPG declines, so GnRH pulses speed up, and FSH secretion increases.
* FSH rescues another cohort of follicles to start development -\> The cycle restarts
337
What 3 hormones does the corpus luteum secrete?
* Progesterone
* Estradiol
* Inhibin
338
What are the effects of progesterone, estradiol and inhibin on the hypothalamo-pituitary-gonadal (HPG) axis?
* Progesterone -\> Inhibitory
* Estradiol -\> Inhibitory when secreted by corpus luteum after ovulation, otherwise stimulatory
* Inhibin -\> Inhibitory
339
What can prevent death of the corpus luteum?
Human chorionic gonadotrophin (hCG)
340
How is muscular activity in the oviduct triggered during the menstrual cycle?
* High levels of estradiol at the end of the follicular phase and in the luteal phase cause muscular activity in the oviduct.
* Its fimbriated end becomes closely apposed to the site of ovulation, ciliated epithelium, wafts the ovulated oocyte into the tube.
341
What are the layers of the uterus wall?
* Myometrium -\> The muscle layer
* Endometrium -\> The overlying epithelial layer on top of the myometrium
342
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
343
What are the two phases of the change of histological structure of the uterus during the menstrual cycle?
* Proliferative phase -\> Before ovulation
* Secretory phase -\> After ovulation
344
Draw how the vasculature of the uterus lining changes during the menstrual cycle.
345
How do these hormones affect uterine vasculature:
* Estradiol
* Progesterone
* Prostaglandins
* Estradiol: Proliferation and spiral artery development
* Progesterone: Glandular secretion
* Prostaglandins: Arterial spasm + Uterine muscle spasm
346
Summarise the effects of estradiol on the reproductive system.
* Local effects within the ovary
* Effects on the uterine tube/uterus stimulating the proliferative phase of the endometrium, and on the cervix/vagina
* Feedback influences on the pituitary and hypothalamus:
* If produced by follicle just after ovulation, then it inhibits the secretion of FSH.
* Later, the rapidly rising levels of estradiol produced by the dominant follicle increase LH production (LH surge) just before ovulation.
347
Summarise the effects of inhibin on the reproductive system.
* Local actions to stimulate production of androgens by the theca
* Endocrine action to suppress FSH secretion by the pituitary (i.e. negative feedback on HPG axis)
348
Summarise the effects of progesterone on the reproductive system.
* On the uterus to induce the secretory phase of endometrial activity.
* On the pituitary and hypothalamus to cause negative feedback, slowing the GnRH pulses and preventing further follicle recruitment and development.
349
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.
350
What causes menopause to happen?
It is when all of the ovarian follicles is depleted.
351
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.
352
What chemical class of hormones are estrogens, inhibin and progesterone?
* Estrogens and progesterone -\> Steroid hormones
* Inhibin -\> Peptide hormone
353
What are the symptoms of menopause?
* Hot flushes, night sweats, irritable, poor sleep
* Post-menopause risk of osteoporosis and hypertension
354
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.
355
Summarise the hormonal changes, follicular changes and uterine changes during the menstrual cycle.
