Lecture 5 and 6: Male Tract and Endocrine Control I and II

Question 1

Testis is an ____ and ____ gland

Answer 1

Exocrine (secretory product = spermatozoa)

Endocrine (secretory product = mainly testosterone)

Question 2

What is the overall pathway of sperm?

Answer 2

• 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.

Question 3

Describe the cell types in the tests

Answer 3

1. Gonocytes
   
   • =Primordial germ cells
   • primitive germ cells that become spermatogonia
   • Only present in early life- up to minipuberty
2. Spermatogonia
   
   • Germ cells
   • Deferentiated to produce sperm
   • Pre-sperm cells that replicate by mitosis
3. 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
4. Leydig cells
   
   • Sit outside the Seminiferous tubules
   • Main product is androgen
5. Myoid cells
   
   • Contractile

Question 4

What cells in the testes differentiate to become sperm?

Answer 4

Spermatogonia

Germ cells

Deferentiated to produce sperm

Question 5

What cells in the testes nurse the developing pre-sperm cells?

Answer 5

Sertoli cells

Question 6

What are the interstitial cells in the testes that produce androgen?

Answer 6

Leydig cells

Question 7

What is this a cross section of?

Answer 7

Seminiferous tubule

Question 8

Label this cross section of Seminiferous tubule

Answer 8

1. leydig
2. basement membrane
3. spermatognium
4. primary spermatocyte
5. secondary spermantocyte
6. spermatid
7. sperm cell or spermatozoon
8. lumen of seminiferous tubule

Question 9

Describe Primordial germ cells

• what they become
• when they’re first seen
• where they’re found

Answer 9

• 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.

Question 10

•Question if an embryo is 21 days post conception what is its gestational age?

Answer 10

5 weeks gestational age

Because conception occurs around 14 days after LMP (last menstrual period)

Question 11

How do we date pregnancies?

Answer 11

Last Menstrual period (or with ultrasound now)

Question 12

What is the difference between post-conception age and LMP?

Answer 12

Conception occurs around 14 days after LMP (last menstrual period)

So 5 weeks LMP = 3 weeks post conception.

Question 13

Describe Germ cell migration.

Answer 13

• 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.

Question 14

When the Primordial Gern cells (PGCs) arrive at the gonads, they’re called ______

Answer 14

Gonocytes (eventually turn into sperm)

Question 15

What forms spermatogonia?

Answer 15

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

Question 16

What are Seminiferous Tubules?

Answer 16

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.

Question 17

Germ cells are thought to arise from _____

Answer 17

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)

Question 18

Describe Leydig cells

Answer 18

• 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.

Question 19

What occurs at 2 months postpartum?

Answer 19

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.

Question 20

Describe the different hormone levels during mini-puberty

Answer 20

• Testosterone (leydig cells)
• AMH and Inhibin (sertoli dependent cells)

Question 21

What is mini-puberty thought to be important in?

Answer 21

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

Question 22

Sertoli cells nurse cells that promote _______

Answer 22

Sertoli cells nurse cells that promote post mitotis development of sperm precursors

Question 23

Describe the Anatomimcal role of the sertoli cells

Answer 23

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

Question 24

Sertoli cells are important for… (4)

Answer 24

• nourishing spermatogonia
• resorbing the e_xcess cytoplasm_ –residual body
• Producing seminiferous tubule fluid
• Maintaining the spermatogonialstem cell niche

Question 25

The very thin arms of the sertoli cells ______

Answer 25

The very thin arms of the sertoli cells wrap around spermatids (process of terming into sperm)

Question 26

The number of Sertoli cells is proprotional to_______

Answer 26

The number of Sertoli cells is proportional to the s_perm production capacity_ of the seminiferous tubule.

Question 27

The number of sertolicells does or does not increase after puberty

Answer 27

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).

Question 28

Describe the process of the moving testes

Answer 28

•Descent of the testis occurs in two phases

1) The transabdominal abdominal (10-15 weeks)
2) The Inguino-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

Question 29

What is the blood-tetis barrier important for?

Why is it important?

Answer 29

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).

Question 30

Where are the gonadal ridges?

Answer 30

Testis form in the gonadal ridges in the lumbar region of the abdomen suspended between two ligaments the caudal and the gubernaculum

Question 31

What is the word for “failure of the testes to decend”?

Answer 31

Cryptorchidism

Question 32

Describe Cryptochidism

Answer 32

•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

Question 33

What is the clinical significance of cryptorchidism

Answer 33

•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.

Question 34

What are the 3 broad changes in the testes at puberty in males?

Answer 34

• Marked increase in proliferation of spermatogonia
• Cords develop a lumen –become seminiferous tubules
• Beginning of sperm production

Question 35

Where does spermatogenesis occur?

Answer 35

Only in the seminiferous tubues of the testes (only occurs after puberty)

Question 36

Name the 3 phases to spermatogenesis

Answer 36

1) Mitotic division
2) Meiotic divison
3) Cytodifferentiation

Question 37

Describe the process of Spermatogenesis

Answer 37

• 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.

Question 38

These mitotic divisions occur in the ________ of the seminiferous tubules

Answer 38

These mitotic divisions occur in the basal compartment (between basemenet membrane and where the tight junctions form) of the seminiferous tubules

Question 39

Spermatogonia have ____chromosomes

Answer 39

Spermatogonia have 46 chromosomes

Question 40

In the adluminal compartment the cells are called ______, they undergo _____

Answer 40

In the adluminal compartment the cells are called primary spermatocytes –they undergo meiosis

Question 41

primary spermatocytes has n____

Answer 41

primary spermatocytes has n-46

Question 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.

Answer 42

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.

Question 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.

Answer 43

The final process in spermatogenesis is spermiogenesisin which the round spermatids differentiate their shape and become spermatozoa (Sperm).

Question 44

In the absence of _______spermiogenesis does not occur and spermatogenesis arrests after ______. The transition from round spermatids to elongated spermatids does not happen.

Answer 44

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.

Question 45

What are the names and number of chromosomes of each cell that eventually becomes a sperm.

Answer 45

• 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)

Question 46

What are the structures on a mature sperm?

Answer 46

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)

Question 47

Describe the Hormonal control of spermatogenesis

Answer 47

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

Question 48

______do not develop into sperm without _______

Answer 48

Spermatogonia do not develop into sperm without testosterone

Question 49

What are some secondary sexual characteristics of dihydrotestosterone

Answer 49

1) Promote Aggressiveness
2) Libedo, sex drive
3) Hair growth
4) Baldness

Question 50

Describe the Negative feedback of the hormonal control of spermatogenesis

Answer 50

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

Question 51

What is the cycle of the seminiferous epithelium

Answer 51

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.

Question 52

The spermatogonia stem cells undergoes division at regulated intervals (not all the time). In humans it’s every ~__days.

Answer 52

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

Question 53

If the cycle of the seminiferous epithelium is always the same length of time how do we get a constant supply of sperm?

Answer 53

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.

Question 54

Label

Answer 54

Question 55

Describe the anatomical features of the Epididymis

Answer 55

• 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

Question 56

Decribe the functional features of the epididymis

Answer 56

• Sperm spend 10-14 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.

Question 57

Sperm gain the ability for _____and ______in the epididymis.

Answer 57

Sperm gain the ability for motility and fertilisation in the epididymis.

Question 58

What is the main function of the vas deferens

Answer 58

• The vas deferens are the m_ajor site of sperm storage in men._
• The VD is about 45 cm long.

Question 59

Describe the Anatomical features of the Vas deferens

• layers
• unique areas

Answer 59

• 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 sperm storage.
•This region is called the ampulla.

Question 60

What are the names of the 2 accessory glands

Answer 60

1) Seminal Vesicles (used to be thought to be the sight of sperm storage)
2) Prostate gland

Question 61

Describe the anatomical features of the seminal vesicles

Answer 61

• 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.

​

Question 62

The ____ joins with the vas deferens to form the ______

Answer 62

The excretory duct joins with the VD to form the ejaculatory duct.

Question 63

What does the seminal vesicles produce?

Answer 63

• 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

Question 64

_______, a Zn2+binding protein, is the major protein produced by the seminal vesicles.

Answer 64

Semenogelin, a Zn2+binding protein, is the major protein produced by the seminal vesicles.

Question 65

Describe the Function of the Prostate gland

Answer 65

• 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.

Question 66

What is the function of the PSA? (

Answer 66

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.

Question 67

What are the different zones of the prostate gland?

Answer 67

• 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 zone 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

Question 68

What are the ‘parts’ of the penis?

Answer 68

• 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.

Question 69

What are the stages of an erection?

Answer 69

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.

Question 70

How does sildenafil work?

Answer 70

• 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.

Question 71

Viagra is not useful if erectile dysfunction occurs because of ….

Answer 71

Viagra is not useful if erectile dysfunction occurs because of parasympathetic nerve damage because there is no stimulation of NO and subsequent cGMP production.