Lecture 5 and 6: Male Tract and Endocrine Control I and II Flashcards
(71 cards)
1
Q
Testis is an ____ and ____ gland
A
Exocrine (secretory product = spermatozoa)
Endocrine (secretory product = mainly testosterone)
2
Q
What is the overall pathway of sperm?
A
- The testes are where sperm are manufactured in the scrotum.
- The epididymis is a tortuously coiled structure topping the testis, and it receives immature sperm from the testis and stores it several days.
- When ejaculation occurs, sperm is forcefully expelled from the tail of the epididymis into the deferent duct. (v_as deferen_s)
- Sperm then travels through the deferent duct through up the _spermatic cord i_nto the pelvic cavity, over the ureter to the prostate behind the bladder.
- Here, the vas deferens joins with the s_eminal vesicle_ to form the ejaculatory duct, which passes through the prostate and empties into the urethra.
- When ejaculation occurs, rhythmic muscle movements propel the sperm forward.
3
Q
Describe the cell types in the tests
A
- Gonocytes
- =Primordial germ cells
- primitive germ cells that become spermatogonia
- Only present in early life- up to minipuberty
- Spermatogonia
- Germ cells
- Deferentiated to produce sperm
- Pre-sperm cells that replicate by mitosis
- Sertoli cells
- Epithelial cells
- Nurse cells- help development of pre-sperm cells.
- Lumen of tubule help developing pre-sperm cells
- Increase in number during minipuberty
- Leydig cells
- Sit outside the Seminiferous tubules
- Main product is androgen
- Myoid cells
- Contractile
4
Q
What cells in the testes differentiate to become sperm?
A
Spermatogonia
Germ cells
Deferentiated to produce sperm
5
Q
What cells in the testes nurse the developing pre-sperm cells?
A
Sertoli cells
6
Q
What are the interstitial cells in the testes that produce androgen?
A
Leydig cells
7
Q
What is this a cross section of?
A
Seminiferous tubule
8
Q
Label this cross section of Seminiferous tubule
A
- leydig
- basement membrane
- spermatognium
- primary spermatocyte
- secondary spermantocyte
- spermatid
- sperm cell or spermatozoon
- lumen of seminiferous tubule
9
Q
Describe Primordial germ cells
- what they become
- when they’re first seen
- where they’re found
A
- Primordial germ cells (PGCs) will become either sperm or oocytes
- PGCs are first seen around 3-4 weeks post-conception
- PGCs are first found in the yolk sac of the extraembryonic tissues and migrate to the gonadal ridges (near the developing kidney) via the hind gut.
10
Q
•Question if an embryo is 21 days post conception what is its gestational age?
A
5 weeks gestational age
Because conception occurs around 14 days after LMP (last menstrual period)
11
Q
How do we date pregnancies?
A
Last Menstrual period (or with ultrasound now)
12
Q
What is the difference between post-conception age and LMP?
A
Conception occurs around 14 days after LMP (last menstrual period)
So 5 weeks LMP = 3 weeks post conception.
13
Q
Describe Germ cell migration.
A
- Stem cell factor (a growth factor) seems to be important in driving migration and if there is inadequate SCF the PGCs die. So PGCs that wander away from the correct path of migration should be eliminated by apoptosis. (so they only end up in the gonads) (avoid ectopic PGCs).
- While migrating, PGCs follow fine enteric nerves and do not always enter or stop at the testes.
- There are reports of germ cells developing ectopically –e.g. in the pancreas where they form oocytes.
- Ectopic germ cells may be the origin of germ cell tumours outside of the testes.
14
Q
When the Primordial Gern cells (PGCs) arrive at the gonads, they’re called ______
A
Gonocytes (eventually turn into sperm)
15
Q
What forms spermatogonia?
A
1) Primordial Germ cells arrive in the (male) gonad = now called gonocytes
2) The gonocytes turn into spermatogonia (have different developmental stages as stem cells)- change not just in puberty but earlier on in life
16
Q
What are Seminiferous Tubules?
A
Seminiferous tubules are located within the testes, and are the specific location of meiosis, and the subsequent creation of male gametes, namely spermatozoa.
The epithelium of the tubuleconsists of a type of sustentacular cells known as Sertoli cells, which are tall, columnar type cells that line the tubule.
17
Q
Germ cells are thought to arise from _____
A
These are thought to arise from PGCs (primordial germ cells)
93% of germ cell tumours are found in the testis (4% in the ovaries, others are ectopic)
18
Q
Describe Leydig cells
A
- In adults and fetuses testosterone is produced by the Leydig cells
- Initial production by embryonic Leydig cells not dependent on stimulation by Testosterone 7-8 weeks (sex differentiation occurs in ¬7-8 weeks gestation)
- Approximately 1_4 weeks gestatio_n production of testosterone becomes LH (pituitary) /hCG(placenta) dependent
- Embryonic Leydig cells are derived from different progenitors to adult Leydig cells. Adult Leydig cells differentiate from stem cells at puberty.
19
Q
What occurs at 2 months postpartum?
A
Mini puberty
Sudden surge in testosterone secretion (then drops off at 3-4 months)
At post-puberty, the leydig cells become responsive to LH and you start to get adult level of testosterone.
20
Q
Describe the different hormone levels during mini-puberty
A
- Testosterone (leydig cells)
- AMH and Inhibin (sertoli dependent cells)
21
Q
What is mini-puberty thought to be important in?
A
Not certain
- masculinising the neonatal brain
- Promoting Sertoli cell proliferation
- Promoting differentiation of gonocytesinto dark AD-spermatogonia
- This may have implications for the timing of orcidoplexy
22
Q
Sertoli cells nurse cells that promote _______
A
Sertoli cells nurse cells that promote post mitotis development of sperm precursors
23
Q
Describe the Anatomimcal role of the sertoli cells
A
Sertoli cells nurse cells tha_t promote post mitotis development_ of sperm precursors
Line the inside of the seminiferous tubules
Create the blood testis barrier
24
Q
Sertoli cells are important for… (4)
A
- nourishing spermatogonia
- resorbing the e_xcess cytoplasm_ –residual body
- Producing seminiferous tubule fluid
- Maintaining the spermatogonialstem cell niche
25
The very thin arms of the sertoli cells \_\_\_\_\_\_
The very thin arms of the sertoli c**ells wrap around spermatids (process of terming into sperm)**
26
The number of Sertoli cells is proprotional to\_\_\_\_\_\_\_
The number of Sertoli cells is proportional to the s_perm production capacity_ of the seminiferous tubule.
27
The number of sertolicells **does or does not i**ncrease after puberty
The number of sertoli cells **does not** increase after puberty!
So if your sertoli cells do not reach an adaequate number following the mini-puberty and then puberty, then you will suffer from oligospermia (reduced sperm content).
28
Describe the process of the moving testes
•Descent of the testis occurs in two phases
1) The **transabdominal abdominal** (10-15 weeks)
2) The I**nguino-scrotal** (25-35 weeks)
•Testis form in the _gonadal ridge_s in the lumbar region of the abdomen suspended between _two ligaments_ the caudal and the gubernaculum
**•Transabdominal phase:**
•As the e_mbryo/fetus grows_ the _gubernaculum does not_ elongate and under the influence of testosterone the _caudal ligament regresses_
•_INSL-3 (insulin-like -3)_ causes _migration of the gubernaculum towards,_ and d_ilation of, the inguinal canal_
•INSL-3 is a constitutively expressed product of the Leydig cells.
**•Inguino-scrotal phase:**
Androgen is important
29
What is the blood-tetis barrier important for?
Why is it important?
The sertoli cells line the seminiferous tubules and form the blood-testis baarrier
Important for _fertility_ and p_revention of antisperm antibody_ production.
No blood vessles behind the seminifeous tubules (therefore is an immune-previledged area). The sertoli cells are themselves Immune-priveledged and can be transplanted into non-priveledged sites- this actively suppresses immune response- they also support surival of other cells e.g. islet cells.
This is important because in a female fetus, the egg is formed during the period where tolerance (when your body knows what is part of you) is developing (6 months of gestation). However in boys, sperm is first developed in puberty. Therefore central tolerance occurs before the sperm is formed. For a boy, the immune has not been exposed to sperm antigens. So if you allow the sperm to be exposed to the immune system, the boy would develop autoimmunity. (e.g. after vasectomy, the immune system can be exposed to the sperm, and can cause infertility).
30
Where are the gonadal ridges?
Testis form in the gonadal ridges in the lumbar region of the abdomen suspended between two ligaments the caudal and the gubernaculum
31
What is the word for "failure of the testes to decend"?
Cryptorchidism
32
Describe Cryptochidism
_•Failure to descend_ –cryptorchidism (crypt = hidden)
•unilateral or bilateral
_Incomplete_
•maldescent(goes to anterior abdominal wall, perineum, or thigh -ectopic sites)
* Affects ~1-9% at full term, 30% of premature male babies.
* Incidence varies widely e.g. boys in Demark are four times more likely the be cryptorchid than boys in Finland. (Gurney et al Risk factors for cryptorchidism.
* _Most self correct,_ within 3 months
* Can correct surgically -_orchidopexy_
33
What is the clinical significance of cryptorchidism
•Failure to descend leads to
1) **Infertility** –due to excess temperature (Spermatogenesis requires a lower temperature which is found in the scrotum but not the abdomen)
2) Is one of the few known risk factors for **testicular cancer**
•Cryptorchidmen have a _3-4 fold increased risk of testicular cancer_
* Important to check for testes in scrotal sacs at birth
* Breast-feed infants are less likely to remain cryptorchidthan non-breast-fed infants.
34
What are the 3 broad changes in the testes at puberty in males?
* Marked increase in proliferation of _spermatogonia_
* Cords develop a lumen –become _seminiferous tubules_
* Beginning of _sperm production_
35
Where does spermatogenesis occur?
Only in the seminiferous tubues of the testes (only occurs after puberty)
36
Name the 3 phases to spermatogenesis
1) Mitotic division
2) Meiotic divison
3) Cytodifferentiation
37
Describe the process of Spermatogenesis
* At puberty the primary germ cells are _reactivated_
* spermatogonial stem cells.
* The spermatogonia divide by _mitosis_.
* _1 daughter cell remains undifferentiated_ -to maintain the stem cell population.
* The other daughter cell _continues to divide by mitosis_ forming **spermatogonia**. The spermatogonia continue to divide by mitosis.
* These m_itotic divisions_ occur in the b_asal compartment_ (between basemenet membrane and where the tight junctions form) of the seminiferous tubules
* Spermatogonia have _46 chromosomes_
* When the mitotic divisions are complete the _spermatogonia move_ between adjacent Sertoli to the a_dluminal compartment_ of the seminiferous tubules.
* In the adluminal compartment the cells are called **primary spermatocytes** –they undergo _meiosis_
* Each of these primary _spermatocytes has n-46_
* During meiosis I the DNA content doubles -each of the spermatocytes still has _46 chromosomes._ (meiosis I)
* At the end of meiosis I the cells are called **secondary spermatocytes** (these have _23 chromosomes_ each with two chromatids).
* Secondary spermatocytes then divide very rapidly -_meiosis II_ -to give four **spermatids** each with _23 chromosomes._
* Spermatids are still round cells and have a round morphology. Round spermatids.
* The final process in spermatogenesis is **spermiogenesisin/cytodifferentiation** which the r_ound spermatids_ differentiate their shape and become **spermatozoa** (Sperm).
* Unnecessary cytoplasm is shed as the residual body (sertoli cells eat this)
* Sperm move into the lumen of the seminiferous tubules
* In the _absence of androgen_ spermiogenesis does not occur and spermatogenesis arrests after meiosis. The transition from round spermatids to elongated spermatids does not happen.
38
These mitotic divisions occur in the ________ of the seminiferous tubules
These mitotic divisions occur in the **basal compartment** (between basemenet membrane and where the tight junctions form) of the seminiferous tubules
39
Spermatogonia have \_\_\_\_chromosomes
Spermatogonia have **46** chromosomes
40
In the adluminal compartment the cells are called \_\_\_\_\_\_, they undergo \_\_\_\_\_
In the adluminal compartment the cells are called **primary spermatocytes** –they undergo **meiosis**
41
primary spermatocytes has n\_\_\_\_
primary spermatocytes has **n-46**
42
At the end of meiosis I the cells are called _____ (these have \_\_\_\_\_chromosomes each with two chromatids).
\_\_\_\_\_\_\_\_ then divide very rapidly -meiosis II -to give four \_\_\_\_\_\_each with \_\_\_chromosomes.
At the end of meiosis I the cells are called **secondary spermatocytes** (these have 23 chromosomes each with two chromatids).
**Secondary spermatocytes** then divide very rapidly -meiosis II -to give four **spermatids** each with **23** chromosomes.
43
The final process in spermatogenesis is \_\_\_\_\_\_\_which the round spermatids differentiate their shape and become \_\_\_\_\_\_(Sperm).
In the absence of androgen spermiogenesis does not occur and spermatogenesis arrests after meiosis. The transition from round spermatids to elongated spermatids does not happen.
The final process in spermatogenesis is **spermiogenesisin** which the round **spermatids** differentiate their shape and become **spermatozoa** (Sperm).
44
In the absence of \_\_\_\_\_\_\_spermiogenesis does not occur and spermatogenesis arrests after \_\_\_\_\_\_. The transition from round spermatids to elongated spermatids does not happen.
In the absence of **androgen** spermiogenesis does not occur and spermatogenesis arrests after **meiosis**. The transition from round spermatids to elongated spermatids does not happen.
45
What are the names and number of chromosomes of each cell that eventually becomes a sperm.
* Spermatogonial stem cells (n=2)
* Spermatogonia(n=2 divide by mitosis, basal compartment of the tubules)
* Primary spermatocytes(in adluminal compartment n=2, divide by meiosis I)
* Secondary spermatocytes-two chromatids meiosis II)
* Spermatids (n=1, begin to cytodifferentiate/spermiogenesis)
* Spermiogenesisis androgen-dependent.
* Sperm (n=1, move to lumen of tubules and exit the tubules)
46
What are the structures on a mature sperm?
1) Tail
2) Mid piece (packed with mitochondria- engine room)
3) Nucleus in the Head of sperm (tightly packed)
4) Acrosome on top of head (lots of receptors)
47
Describe the Hormonal control of spermatogenesis
1. _GnRH_ is released in the _hypothalamus_ and it travels down the portal blood
2. It acts on the _gonadotrophs_ in the Anterior pituitary. The gondaotrophs release _LH and FSH_
3. _LH_ travels via the blood to the testes where it acts on the leydig cells (outside of the seminiferoust tubules) to produce **Testosterone**
4. The _testosterone_ is responsible for producing secondary sexual charactersitics but the secondary sexual characterisitics are produced by **Dihydrotestosterone** (formed from testosterone)
5. _FSH_ travels via blood to _sertoli_ cells inside the serminferous tubues (in direct contact with spermatogonia). This does a lot of things, one is Protein synthesis (**androgen binding protein**)
6. The ABP carries steroids (e.g. testosterone). Some goes either into or out of the seminifeous tubule. The ones that go in, maintain concentration of androgen that freely crosses the membranes and keeps a good concentration of androgen in the tubules. Others leave into the blood and helps to transport the DHT (dihydrotestosterone) around the body.
7. Under the stimualtion of FSH, the last stage of spermatogenesis occurs
48
\_\_\_\_\_\_do not develop into sperm without \_\_\_\_\_\_\_
**Spermatogonia** do not develop into sperm without **testosterone**
49
What are some secondary sexual characteristics of dihydrotestosterone
1) Promote Aggressiveness
2) Libedo, sex drive
3) Hair growth
4) Baldness
50
Describe the Negative feedback of the hormonal control of spermatogenesis
**Leydig cells** produce **Testosterone**/Androgens travels back with ABP back to the hypothalamus and pituitary to down-regulate the production of _FSH_ and _LH_
Also production of **inhibin** from **sertoli** cells result in reduction of production in _FSH_
51
What is the cycle of the seminiferous epithelium
The _time taken for a sperm_ to be produced from a germ cell is constant and Characteristic in each species
The spermatogonia stem cells undergoes division at regulated intervals (not all the time). In humans it's every ~16 days. (~16 days between successive waves of developing spermatozoa)
Thus, at any one point on a tubule, the interval between the release of successive waves of sperm into the lumen is 16 days.
52
The spermatogonia stem cells undergoes division at regulated intervals (not all the time). In humans it's every ~\_\_days.
The spermatogonia stem cells undergoes division at regulated intervals (not all the time). In humans it's every ~**16** days.
•In each segment of a tubule along it’s length spermatogenesis is just ahead of the preceding segment.
The Cycle of the seminiferous epithelium
53
If the cycle of the seminiferous epithelium is always the same length of time how do we get a constant supply of sperm?
We have constant supply of sperm.
* The spermatogenicwave and cycle of the seminiferous epithelium are responsible for the continuous supply!
* In _each segment_ of a tubule along it’s length spermatogenesis is just ahead of the preceding segment.
54
Label
55
Describe the anatomical features of the Epididymis
* A _comma shaped_ organ running superior and posterior to the testes
* Efferent tubules of the _testis/rete testis_ drain into the _head of the epididymis_
* It is about 7.5 cm long with a single convoluted tubule of about 4-6m in length
56
Decribe the functional features of the epididymis
* Sperm spend 1_0-14 days_ passing through the epididymis during which time they are **_concentrated_** 100 fold from 5x 107to 5 x109/ml
* _Fluid resorptio_n is mediated by _stereocillia_
* Sperm _gain the ability f_or **motility** and **fertilisation** in the epididymis.
57
Sperm gain the ability for \_\_\_\_\_and \_\_\_\_\_\_in the epididymis.
Sperm gain the ability for **motility** and **fertilisation** in the epididymis.
58
What is the main function of the vas deferens
* The vas deferens are the m_ajor site of sperm storage in men._
* The VD is about 45 cm long.
59
Describe the Anatomical features of the Vas deferens
- layers
- unique areas
* The VD consist of _three muscular layers_ surrounding the epithelial lining. (tells us peristalsis occurs here)
* Inner longitudinal layer
* Middle circular layer
* Outer longitudinal layer.
•At the epididymal end the lumen is a r_elatively simple tube._
Just _prior to the prostate gland_ the lumen becomes _enlarged_ and folded with many crypts
•This allows additional s**perm storage.**
•This region is called the **ampulla**.
60
What are the names of the 2 accessory glands
1) Seminal Vesicles (used to be thought to be the sight of sperm storage)
2) Prostate gland
61
Describe the anatomical features of the seminal vesicles
* _Highly folded_ tubular/pouch-like glands.
* Surrounding the secretory tissue is extensive smooth muscle.
* **The excretory duct joins with the VD to form the ejaculatory duct.**
****
62
The ____ joins with the vas deferens to form the \_\_\_\_\_\_
The **excretory duct** joins with the VD to form the **ejaculatory duct.**
63
What does the seminal vesicles produce?
* Secrete an _alkaline fluid_ containing _fructose_ which is the major _energy_ source for sperm. (vagina is acidic)
* **_Semenogelin_**, a Zn2+binding protein, is the major protein produced by the seminal vesicles.
* _Semen clots immediately_ after ejaculation with _semenogelinI_ ( and II) being the m_ajor constituent of the clo_t (fibronectin is also important).
* Seminal vesicles are relatively unsusceptible to tumour growth
64
\_\_\_\_\_\_\_, a Zn2+binding protein, is the major protein produced by the seminal vesicles.
**Semenogelin**, a Zn2+binding protein, is the major protein produced by the seminal vesicles.
65
Describe the Function of the Prostate gland
* Doughnut-shaped organ the size of a golf ball
* Surrounds the prostatic urethra
* Secretes a _milky coloured slightly acidic_ (some suggest it is slightly alkaline) fluid
* A major protein in the prostatic secretions is _prostate specific antigen_ –PSA used in cancer screening in some countries –not NZ
* PSA breaks down the seminal coagulum (prostatic fluid breaks down the coagulum so after a ejaculate, within 10-15 minutes the coagluate breaks down, allowing the semen to be released.
66
What is the function of the PSA? (
**Prostatic Specific Antigen** breaks down the _seminal coagulum_ (prostatic fluid breaks down the coagulum so after ejaculation, within 10-15 minutes the coagluate breaks down, allowing the semen to be released.
67
What are the different zones of the prostate gland?
* The prostate may be divided into zones
* **Central zone** surrounds the urethra 25% of glands –resistant to carcinoma
* **Peripheral zone** surrounds the central zone, 70% of glands –main site of carcinoma
* **Transition zon**e 5% of glands surrounds the proximal prostatic urethra –major site of benign hyperplasia
* **Anterior zone** fibromuscular tissue no glands
* Urethra goes through the centre of the prostate gland
68
What are the 'parts' of the penis?
* Consists of two corpora cavanosa
* One corpus spongiosium
•Erection occurs following sexual stimulation
1) Parasympathetic nerve activity induces acetylcholine release
2) The acetylcholine induces NO release by endothelial cells of the corpora
3) NO induces cGMP production which in turn causes vasodilation
4) The corpora relax and engorge with blood
5) Venous outflow is reduced increasing engorgement/erection
To prevent the urethra from collapsing, we have the corpus spongiosum. It is a circular erectile structure that surrounds the urethra. The corpus spongiosum is also filling up with blood. It prevents the crushing of the urethra.
69
What are the stages of an erection?
The penis consists of
* Consists of two corpora cavanosa
* One corpus spongiosium
•Erection occurs following sexual stimulation
1) Parasympathetic nerve activity induces _acetylcholine_ release
2) The acetylcholine induces _NO release_ by endothelial cells of the _corpora cavanosa_
3) _NO induces cGMP_ production which in turn causes vasodilation
4) The _corpora cavanosa relax_ and engorge with blood
5) _Venous outflow is reduced_ increasing _engorgement/erection_
To prevent the urethra from collapsing, we have the corpus spongiosum. It is a circular erectile structure that surrounds the urethra. The corpus spongiosum is also filling up with blood. It prevents the crushing of the urethra.
70
How does sildenafil work?
* Viagra -used to _enhance erection_
* blocks the action of _type V phosphodiesterase_
* Phosphodiesterase breaks down cGMP
* Inhibiting phosphodiesterase i_ncreases levels of cGMP –vasodilation_
* Viagra is _not useful_ if erectile dysfunction occurs because of _parasympathetic nerve damage_ because there is _no stimulation of NO_ and subsequent cGMP production.
71
Viagra is not useful if erectile dysfunction occurs because of ....
Viagra is not useful if erectile dysfunction occurs because of **parasympathetic nerve damage** because there is no stimulation of NO and subsequent cGMP production.
