Lecture 5 + 6 - 2017 Flashcards

1
Q

How is the testes an exocrine gland?

A

It secretes spermatozoa.

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2
Q

How is the testes an endocrine gland?

A

It secretes testosterone.

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3
Q

What happens in the early stages of testes development?

A

Germ cells are set outside the developing embryo (on the yolk sac - posterior side). These have to migrate to the embryo and they start to form the testes.

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4
Q

After the germ cells migrate to the embryo what happens?

A

They migrate up and around to the developing hindgut (connected to the dorsal part of the mesentery) and split outside of where the aorta is developing and come to lie on either side of the genital ridges (pelvic cavity). The germ cells come in and take up with the epithelial cells that cover the genital ridge. The epithelial cells wrap around the germ cells.

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5
Q

What do the epithelial cells form?

A

Sertoli cells - which nourish and feed developing stages of germ cells (spermatogonia).

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6
Q

What does the interstitial tissue between cords form?

A

Leydig cells and myoid cells.

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7
Q

What do the germ cells form?

A

Spermatogonia.

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8
Q

When do the testis descend?

A

7-8 months in utero (7-8month fetus).

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9
Q

How does this occur?

A

The testes go from an intra-abdominal position to a position outside of the body. It occurs via a ligament (gubernaculum) that shortens and drags the testicles down, this is all under the control of AMH.

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10
Q

What are gonocytes?

A

Primitive germ cells that become spermatogonia (only present in ealry life).

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11
Q

What are spermatogonia?

A

They come from germ cells that are essentially differentiated pre-sperm cells that replicate by mitosis.

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12
Q

What are sertoli cells?

A

These come from epithelial cells, that sit in the lumen of tubule that help to develop pre-sperm cells.

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13
Q

What are leydig cells?

A

These come from interstitial stromal tissue and their function is to produce testosterone.

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14
Q

What are myoid cells?

A

These come from interstitial stromal tissue and their function is to contract.

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15
Q

How does AMH contribute to the descent of testes?

A

Controls movement within the abdominal cavity and down to the inguinal ring.

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16
Q

How does testosterone contribute to the descent of testes?

A

Testosterone controls the movement from the ring to the sac.

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17
Q

What other factors affect the embryonic development of the testes?

A

Stem cell factor is important in driving migration, if there is inadequate SCF then the primordial germ cells will die.

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18
Q

What happens will the primordial germ cells migrate?

A

They follow fine enteric nerves and do not always enter or stop at the testes e.g. ectopic - in the pancreas where they always form oocytes.

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19
Q

Where are germ cell tumours found?

A
  1. 93% in testis.
  2. 4% in ovaries.
  3. 3% are ectopic (not in gonads).
  4. Most common site is in the CNS - keep on migrating and survive into CNS.
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20
Q

Where is testosterone produced?

A

Leydig cells.

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21
Q

Describe the initial production of testosterone by embryonic leydig cells?

A

This initial production is not dependent on stimulation by LH (7-8 weeks).

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22
Q

What happens at 14 weeks gestation in terms of testosterone production?

A

The production of testosterone becomes LH (pituitary)/hCG (placenta) dependent.

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23
Q

List the testosterone levels throughout a boys life?

A
  1. 13-15 weeks = 2ng/ml.
  2. 5-6 months = 0.8ng/ml.
  3. 2 months post partum = 2-3ng/ml (mini puberty).
  4. 3-4 months post partum = 0.5ng/ml.
  5. pre-puberty = 0.1ng/ml.
  6. post-puberty = 2-3ng/ml.
  7. Adult = 3-9ng/ml (4-10mg/daily).
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24
Q

Why is there high levels of testosterone at mini puberty?

A

This is to do with gonadal programming that pre-programmes testicular tissue and gonadal tissue - into a routine so that it occurs at puberty. Also important in causing sertoli cell proliferation and promoting differentiation of gonocytes into dark AD-spermatogonia.

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25
Q

Where do sertoli cells sit?

A

On the basement membrane, they span from the bm to the lumen of the seminiferous tubules.

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26
Q

What do sertoli cells do?

A

They nourish spermatogonia, resorb the excess cytoplasm (residual body), produce seminiferous tubule fluid and mantain the spermatogonial cell niche.

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27
Q

Where are spermatids embedded?

A

Deeply into the sertoli cells.

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28
Q

Describe the sertoli-to-sertoli junctional complex?

A

Tight junction that contributes to the blood-testis barrier. It prevents WBC from sensing developing gametes (perceived as foreign bodies due to genetic cross over).

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29
Q

Describe the sertoli-to-spermatid junctional complex?

A

Adhesion device that resides in deep recess within apical cytoplasm. Germ cells can slide through the tight junction. Before the junction mitosis occurs, after the junction, meiosis and cytodifferentiation occur.

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30
Q

What is the transit time of sperm from the basal lamina to the lumen?

A

74 days.

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31
Q

What is the time between waves of developinbg spermatozoa?

A

16 days.

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32
Q

What is cryptorchidism?

A

Failure of testes to descend.

  1. Unilateral = one testis.
  2. Bilateral = both testes.
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33
Q

What are the types of cryptochidism?

A
  1. Incomplete: testes is on the right track to descend but gets stopped and lodges in inguinal canal.
  2. Maldescent: testes goes to anterior wall of abdomen, perineum or thigh.
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34
Q

What are the consequences of cryptorchidism?

A
  1. Infertility - this is due to the increased temperature in the body. Spermatogonia require lower temperature (2 degrees).
  2. Risk factor for testicular cancer - 3-4 fold increased risk.
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35
Q

What are the four phases of spermatid development?

A
  1. Golgi phase.
  2. Cap phase.
  3. Acrosomal phase.
  4. Maturation phase.
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36
Q

Describe the golgi phase?

A

Spermatids start out as rounded cells and the proteins go into the golgi and accumulate into vesicles which fuse and form pro-acrosomal granules (from acrosome) The pro-acrosomal granules contain digestive enzumes for ZP of egg (important for fertilisation).

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37
Q

Describe the cap phase?

A

The granules (from the golgi phase) keep fusing until they form a cap of acrosomal material (acrosome) which is bound by the membrane.

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38
Q

Describe the acromsomal phase?

A

The shape of the cell starts changing - starts to elongate (centrioles elongate to become a tail) and oval. The acrosome spreads down over the nucleus.

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39
Q

Describe the maturation phase?

A

The spermatids are released into the lumen with the tails of the spermatid in the lumen, with the heads embedded in the sertoli cells. The sertoli cells phagocytose the cytoplasm of the spermatid.

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40
Q

Where does spermatogenesis take place?

A

Seminiferous tubules of the testes.

41
Q

When does spermatogenesis occur?

A

Only after puberty.

42
Q

How many sperm are produced per second?

A

300-600 sperm per gram of testis tissue per second.

43
Q

What are the three phases of spermatogenesis?

A
  1. Mitotic division.
  2. Meiotic division.
  3. Cytodifferentiation.
44
Q

What happens at spermatogenesis?

A

At puberty the germ cells are reactivated. 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.

45
Q

How many chromosomes do spermatogonia have?

A

46.

46
Q

Where does mitotic division occur?

A

Basal compartment of the seminiferous tubules.

47
Q

What happens when the mitotic divisions are complete?

A

The spermatogonia move between adjacent sertoli to the adluminal compartment of the seminiferous tubules. In the adluminal compartment the cells are called primary spermatocytes - they undergo meiosis.

48
Q

What happens during meiosis I?

A

The DNA content doubles - each of the spermatocytes still has 46 chromosomes.

49
Q

What happens at the end of meiosis I?

A

At the end of meiosis ( the cells are called secondary spermatocytes (these have 23 chromosomes each with two chromatids).

50
Q

What happens in meiosis II?

A

Secondary spermatocytes divide very rapidly to give four spermatids; each with 23 chromosomes.

51
Q

What happens in the absence of androgen (in spermiogenesis)?

A

Spermiogenesis does not occur and spermatogenesis arrests after meiosis. The transition from round spermatids to elongated spermatids does not happen.

52
Q

Is testis development dependent on the pituitary?

A

All stages of testis development is dependent on the pituitary.

53
Q

Is the pituitary function dependent on testis?

A

If you remove the testis, there is a rise in LH and FSH, so there is no negative feedback on testosterone. Therefore, the anterior pituitary function is dependent on the testis via the negative feedback.

54
Q

Does exogenous testosterone affect anterior pituitary function?

A

When you add more testosterone, it inhibits GnRH (decrease in GnRH) so there is a decrease in FSH and LH therefore there is a reduce in sperm count (infertile).

55
Q

IS there a direct relationship between LH and testosterone?

A

Yes - as LH is produced it stimulates testosterone and pulses in the same pattern as LH.

56
Q

What does the hypothalamus release?

A

GnRH.

57
Q

What does GnRH act on and what does it release?

A

The anterior pituitary - it causes the release of LH and FSH.

58
Q

Where are LH receptors located?

A

Leydig cells.

59
Q

What does LH act on and what is released?

A

LH binds to LH receptors on the leydig cells. Where cholesterol is converted to progesterone which is converted into Testosterone.

60
Q

What happens to testosterone after being produced in the leydig cells?

A

It is released into the plasma where it acts:
i) negatively on the leydig cell to stop the production of more testosterone.
ii) acts on sertoli cells where it is converted into estrogen or DHT.
It can also be made into DHT at the leydig cell.

61
Q

What does testosterone do?

A

It acts on the epididymis, prostate and seminal vesicles to help with secondary sexual characteristics (sex drive, aggressiveness, hair growth, baldness). DHT is mainly used as it is more active and it can’t be aromatased to estrogen.

62
Q

Where does FSH act on and what is released?

A

Sertoli cells:

  1. Inhibin is produced.
  2. Aromatase which converts testosterone into estrogen.
  3. ABP - androgen binding protein (testosterone is linked to this when it is carried around).
  4. Other proteins.
63
Q

What does inhibin do?

A

It has a negative feedback at the ant pit level on FSH only. It stops FSH from being produced and acting on the sertoli cells.

64
Q

What does estrogen do?

A

It negatively inhibits/feedback on leydig cells, hypothalamus. This is to stop the release of GnRH or to inhibit it from acting on the ant pit.

65
Q

What is the effect of testosterone/DHT on spermatogonesis?

A
  1. Necessary for meiosis - especially prophase of 1st division.
  2. Necessary for spermatid maturation - at higher levels than for meiosis.
  3. Stimulates ABP - so that more testosterone can be carried around.
66
Q

What happens in a man where the testis aren’t functioning (hypogonadal)?

A

There is a decrease in gonadal function which causes a decrease in testosterone, therefore an increase in FSH and LH (loss of negative feedback). This will cause a decrease in germ cells being produced as there is less testosterone available to produce spermatogonia. There is also a decrease in ABP so there is less testosterone able to be carried around.

67
Q

What do you do for a man who is hypogonadal?

A

You give him exogenous testosterone.

68
Q

What is the effect of estrogen in males?

A
  1. Negative feedback control.

2. Enhancing action of androgens - estrogens induce fibromuscular growth in male accessory organs.

69
Q

What happens if there is no estrogen/aromatase does not work in females?

A

Ovarian follicles will start to develop but don’t progress to ovulation. There are peripheral atretic secondary follicles that are similar to polycystic follicles. By 1 year early follicles become seminiferous tubule-like structures and develop sertoli cells that have tight junctions and leydig cells develop in interstitial tissue.

70
Q

What happens if there is no estrogen in males?

A

Spermatogenesis is interrupted - it stops at the early stage of spermatid development.

71
Q

Describe briefly obstructive azoospermia?

A

There is no sperm in the semen due to problems with sperm delivery - something is blocking sperm from being delivered. There can be problems with the ductal system or issues with ejaculation i.e. ducts can be missing or blocked (no vas deferens). FSH levels are normal.

72
Q

Describe hypospermatogenesis?

A

This is where there is a low sperm count. Most males still have FSH in a normal range, however, those with really low sperm counts have really high FSH levels. There is not enough testosterone so there is lack of negative feedback thus an increase in FSH.

73
Q

Describe germinal cell arrest?

A

Spermatogonia do not develop properly.

74
Q

Describe sertoli-cell-only syndrome?

A

This is a rare condition in which there are no germ cells - spermatogonia aren’t produced. There is an increase in FSH levels and inhibin is not produced.

75
Q

What is the epididymis?

A

It is a comma shaped organ that runs superior and poterior to the testis. It is about 7.5cm long with a single convoluted tubule of about 4-6m in length.

76
Q

Where do rete testis drain?

A

Head of the epididymis.

77
Q

Where does sperm maturation occur?

A

Epididymis.

78
Q

How long does it take sperm to pass through the epididymis?

A

1-21 days (roughly 2 weeks).

79
Q

What happens to sperm in the epdidymis?

A
  1. The residual cytoplasm is absorbed.
  2. There are more disulphide bonds formed in structural proteins - this helps to stiffen the sperm and it alters the sperms swimming behaviour (allow sperm to swim in a sinusoidal wave).
  3. Increased surface charge (more negative).
  4. The concentration of sperm increases 100 fold - resorption of fluid (goes from 50million per ml to 5000million per ml).
80
Q

Where are sperm stored?

A

Vas Deferens - the sperm are stored here after leaving the epdidymis.

81
Q

How long is the vas deferens?

A

45cm long.

82
Q

What does the vas deferens consist of?

A

Three muscular layers surrounding the epithelial lining:

  1. Inner longitudinal layer.
  2. Middle circular layer.
  3. Outer longitudinal layer.
83
Q

What is important about the vas deferens just prior to the prostate gland?

A

The lumen becomes enlarged and it is folded with many crypts. This allows for additional sperm storage - region is called the ampulla.

84
Q

What are the seminal vesicles?

A

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.

85
Q

What do the seminal vesicles secrete?

A

Alkaline fluid (pH 7.3) which contains fructose and porstaglandins. It also produces semenogelin - a zinc binding protein that causes the semen to clot immediately after ejaculation.

86
Q

What is the prostate gland?

A

Doughnut shaped organ the size of a golf ball. It surrounds the prostatic urethra.

87
Q

What does the prostate gland secrete?

A

It secretes a milky coloured fluid that consists of:

  • acid phosphatase.
  • citric acid.
  • spermine (polyamine for sperm motility).
  • Fibrinolysin (breaks down the sperm clot).
  • PSA (used to break down the coagulum).
88
Q

What are the prostate gland zones?

A
  1. Central zone - surrounds the urethra, 25% of glands, resistant to carcinoma.
  2. Peripheral zone - surrounds the central zone, 70% of glands, main site of carcinoma.
  3. Transition zone - 5% of glands surrounds the proximal prostatic urethra, major site of benign hyperplasia.
  4. Anterior zone - fibromuscular tissue, no glands.
89
Q

What muscles does the penis consist of?

A
  1. One corpus spongiosium.

2. Two corpora cavanosa.

90
Q

How does an erection occur?

A
  1. PNS activity induces ACh release.
  2. ACh induces NO release bny endothelial cells of the corpora.
  3. NO induces cGMP production which in turn causes vasodilation.
  4. Corpora relax and engorge with blood.
  5. Venous outflow is reduced increasing engorgement/erection.
91
Q

What does viagra do?

A

It enhances erection by blocking the action of type V phosphodiesterase (this breaks down cGMP) - this will increase the levels of cGMP hence increase vasodilation.

92
Q

What do you assess in male infertility?

A
  1. Liquefaction.
  2. Volume.
  3. Sperm concentration.
  4. Motility.
  5. Grade of motility.
  6. Morphology.
  7. Debris.
93
Q

Describe liquefaction assessment?

A

Basically you are testing to see if the sperm liquify’s within 15 minutes.

94
Q

Describe volume assessment?

A

If the total volume is <1ml there is likely a problem.

95
Q

Describe sperm concentration assessment?

A

If the sperm concentration is <15x10 ^ 6 per ml there is likely a problem.

96
Q

Describe grade of motility assessment?

A

0 = twitching.
1 = poor.
2 = moderate forward progress.
3. good forward progress.

97
Q

Describe morphology assessment?

A

There is a considerable range. A male can have up to 70% of his sperm be abnormal but still get fertilisation if sperm count is sufficiently high.

98
Q

Describe debris assessment?

A

there should not be any debris in semen especially WBC.