S4: Spermatogenesis Flashcards

1
Q

Describe path of sperm in male reproductive anatomy

A

When the male ejaculates, the sperm moves out of the testes through the vas deferens and then enters into the prostatic urethra as the ejaculatory duct. The ejaculatory duct is where the vas deferens combines with the seminal vesicle outflow.

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2
Q

What is the function of testes?

A

The testes produce sperm and store it. They are also the site of hormone production that regulates spermatogenesis the principle one being testosterone.

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3
Q

Describe structure of testes

A
  • The testes lie in the scrotum that is outside the body cavity. This might be because it is the optimum temperature for sperm production at 1.5-2.5 degrees below body temperature. It is thought that overheating the testes reduces sperm count.
  • The testes are well vascularised and well innervated.
  • The testis is made up of lobules and each lobule contains tiny coiled up tubes called the seminiferous tubules. There are about 200-300 lobules each containing 400-600 seminiferous tubules.
  • 90% of the testis is actually seminiferous tubules, it is here that is the site of spermatogenesis. Each testis contains 600m of seminiferous tubules and they are tightly coiled.
  • Note smooth muscle cells surround the seminiferous tubules.
  • All the seminiferous tubules in a testis come together to one area one the side called the rete testis. It is here that the sperm is concentrated.
  • The rete testis then leads on to the epididymis, the site of sperm storage and then the vas deferens.
  • The vas deferens will subsequently join the urethra.
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4
Q

What is the normal volume of the testes and measured by?

A

The normal volume of the testes is approximately 15-25ml, and this is measured using an orchidometer.

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5
Q

Describe the anatomy of spermatogenesis (where each stage takes place)

A
  • The sertoli cells are the male equivalent of the granulosa cells and in between the sertoli cells the sperm develop.
  • Around the inner edge of the tubule, the spermatogonium are located and here they divide by mitosis to increase their number, these are A-spermatogonia. Spermatogonia are diploid.
  • There are some B-spermatogonia that commit to meiosis begin to move towards the lumen in between the sertoli cells. They will become haploid and develop their flagella and are eventually released into the lumen.
  • The adluminal compartment opens to allow the passage of spermatogonia prior to completion of meiosis.
  • Until eventually the final mature sperm is released into the seminiferous tubule lumen, it then moves up to the rete testes, to the epididymis and then will be eventually released.
  • There are also the Leydig cell in the testes that lie just outside the seminiferous tubule and produce testosterone.
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6
Q

What is the adluminal compartment and blood testes barrier?

A
  • The Sertoli cells form tight junctions between themselves, this keeps the developing sperm in confined compartments in the tubule. This is called the adluminal compartment. So the sertoli cells divide the tubule into a luminal compartment running through the middle, the interstitial space on the outside world and the adluminal compartments between sertoli cell tight junctions. This keeps the spermatogonia in a specialised environment so they pick up nourishment and secretions from the sertoli cells.
  • The sertoli cells also separate the inside of the tubule to the interstitial space. This forms a blood-testis barrier. This means the immune system never sees the inside of the testis and has never seen the bodies own gametes.
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7
Q

How is the blood testes barrier clinically important?

A

It can become a problem in vasectomy, where some of the contents of the testis can leak into the circulation, the immune system sees the gametes for the first time and makes antibodies against the mans own sperm. This means if the man wants to reverse the vasectomy, it may not work as well as hoped or he may have subfertility, due to antibodies agglutinating his own sperm.

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8
Q

Describe cells of seminiferous tubules

A
  • The walls of the tubule are made of the tall columnar endothelial cells, the Sertoli cells.
  • Between the Sertoli cells laying on the basement membrane are the primary germ cells, the spermatogonia.
  • The spaces inbetween tubules (i.e. on the outside) are filled with blood and lymphatic vessels, as well as the Leydig cells and interstitial fluid.
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9
Q

Name the three main stages of spermatogenesis and decribe them

A
  1. Mitotic proliferation of spermatogonia. This is the Ad (A-dark) spermatogonia that always replace themselves by mitosis. The diploid cells are the spermatogonia.
  2. Meiosis and development of spermatocytes. A small portion of the Ad spermatogonia will however develop into Ap (A-pale) spermatogonia which will then become B spermatogonia. The B-spermatogonia will then commit to meiosis and become primary spermatocytes. After meiosis I they become a secondary spermatocyte and they are now haploid and contain identical sister chromatids. Now enter into meiosis II and become spermatids which are truly haploid with only 23 chromosomes.
  3. Spermiogenesis, elongation, loss of cytoplasm and movement of cellular contents. The spermatids then need to become spermatozoa, so lose their cytoplasm, grow the flagella, and acrosome and this process is called spermiogenesis. The movement into the lumen of the sperm is controlled by sertoli cell secretions and factors produced by sertoli cells are required for the sperm development.
    Right until the end, the germ cells are linked by cytoplasmic bridges, so appear as a chain of germ cells. This is called a syncytium and happening all along the tube.
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10
Q

Compare oogonia and spermatogonia

A
  • All the oogonia are all laid down in the female foetus, spermatogonia are also laid down in the male foetus.
  • The oogonia begin meiosis to make the oocyte, the spermatogonia also begin meiosis to make spermatocyte OR they can divide mitotically to make more spermatogonia.
  • The female cannot make more oocyte by mitosis, she has a finite/limited number that was laid down in foetal life. As the male can replenish his spermatogonia by mitosis he has a lifetime supply of gametes.
  • With the female gametes it is quality over quantity whereas with the male gametes it is quantity over quality.
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11
Q

Compare the female and male hypothalmic/pituitary.gonadal axis

A
  • In terms of hormones the two are actually relatively similar. The male produces more testosterone/DHT, but females do produce some testosterone.
    These are steroids and negatively feedback on the hypothalamus/pituitary to reduce the gonadotrophin levels.
  • The big difference between the two is that the females HPG axis is cyclical, with oestrogen dominating the first half of the cycle and then progesterone dominates the second half after ovulation.
  • In the male the HPG axis is not cyclical, it has exactly the same control mechanism that doesn’t change. It occurs at a steady state, always getting LH and FSH, testes is always stimulated to make sperm and testosterone (mainly) and oestrogen and DHT.
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12
Q

Describe steroid production in the testis (male HPG) and function of them in spermatogenesis

A
  • The hypothalamus releases GnRH that acts on the gonadotrophs of the anterior pituitary, causing release of LH/FSH.
  • The LH binds to the Leydig cells and causes production of testosterone (in females, LH binds to theca cells that produce androgens).
  • The testosterone produced goes around the whole body, bound to androgen binding protein (ABP), only the free testosterone is active at any one time. The testosterone acts on the sertoli cells helping to control their activity and stimulating their function and thus control spermatogenesis.
  • Testosterone also feeds-back and reduces the gonadotrophins.
  • FSH is released from the pituitary in the males, but there are no follicles to stimulate. Instead FSH binds directly to its receptor on the sertoli cells, here it maintains the population of sertoli cells. It also stimulates androgens to be converted to oestrogens by aromatase present in sertoli cells.
  • So FSH enables there to be a normal quantitative sertoli cell population whereas androgens initiate and maintain sperm production.
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13
Q

How do you interfere with negative feedback in male HPG axis and its effect?

A
  • This is through anabolic steroids!
  • The anabolic steroids will feedback on the hypothalamus and pituitary and reduce the secretions of FSH/LH.
  • Reduce LH leads to reduce testosterone production.
  • As FSH maintains the Sertoli cell population reduced FSH leads to testicular atrophy.
  • There is also some aromatase in males as well, this means when there are very high androgens, some will be converted to oestrogens. This causes the growth of breast tissue.
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14
Q

Describe the nervous control of erection and ejaculation

A
  • Both erection and ejaculation are under the control of the autonomic nervous system.
  • The parasympathetics control the beginning and end, the erection and final evacuation of the urethra.
  • Under parasympathetic control at the same time, the venous return of the penis partially constricts. The net result is an increased blood flow into the corpus cavernosum, constricted venous return and higher blood pressure in corpus cavernosum leading to erection.
  • The sympathetic nervous system controls movement of sperm into the epididymis, vas deferens, penile urethra and expulsion of glandular secretions.
  • Somatic nervous system (peroneal branch of pudendal nerve roots S2-S4) causes expulsion of glandular secretions and evacuation of urethra. These are still not under conscious control.
  • (Point and Shoot and Score)
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15
Q

Describe the structure inside the penis

A

The inside of the penis contains highly vascularised tissue called the corpus cavernosum, the cavernosal arteries dilate and blood rushes in. The corpus cavernosum in the diagram above are the two big superior cylindrical columns, whereas the small one underneath is the corpus spongiosum containing the urethra running through it.

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16
Q

Describe the content of ejaculate

A
  • 300 million sperm are produced per day on average, 3,500 per second. There are approximately 120 million sperm in the average ejaculate.
  • The normal ejaculate volume is 1.5ml-6ml. so only about one third to just over a teaspoon full.
  • It is the initial portion of the ejaculate that is most sperm rich, this is important as some people may miss the first part of the ejaculate when giving a semen sample and this can give an incorrect result.
  • Of the 120 million sperm in the ejaculate, 99.9% are lost before reaching the ampulla of the uterine tube, only around 120,000 sperm get near to the egg and only one will enter.
17
Q

Path of sperm as it leaves the epididymis to seminal fluid

A

As the sperm leaves the epididymis and moves up the vas deferens it is only in a very small amount of epididymal fluid. The sperm then gets mixed with other secretions to form the seminal fluid.

18
Q

What does seminal fluid contain?

A

Seminal fluid that is ejaculated consists of secretions from the seminal vesicles, prostate and bulbo-urethral gland combined with epididymal fluid.

19
Q

Describe secretions from bulbourethral gland into seminal fluid

A
  • The very first secretion actually starts secreting before ejaculation, the bulbo-urethral glands.
  • The bulbo-urethral glands produces a clear viscous secretion, high in salt known as pre-ejaculate. This fluid helps to lubricate the inside of the urethra for the spermatozoa to pass through, it also helps neutralise traces of acidic urine (the fluid is alkaline).
    The sperm could be damaged if they went through the urethra and there was too much friction or it was too acidic so the bulbo-urethral glands help prevent this.
  • When there is ejaculation, the sperm are released from the epididymis and move up the vas deferens. At the ampulla, the seminal vesicles add their secretions to the sperm as it enters into the ejaculatory duct.
20
Q

Describe secretions from seminal vesicles into seminal fluid

A
  • These seminal vesicle secretions comprise 50-70% of the ejaculate! It contains proteins, enzymes, fructose, mucus, vitamin C and prostaglandins.
  • The high fructose concentrations in the secretions are important as act as an energy source for sperm. If there is no fructose in a semen sample it indicates a problem with the seminal vesicles.
  • The high pH of the fluid protects against the acidic environment in the vagina.
  • At this point the sperm will be starting to swim.
21
Q

Describe secretions from prostate into seminal fluid

A
  • The prostate secretes a milky or white fluid (giving semen its colour) and makes up roughly 30% of the seminal fluid.
  • The protein content of the prostate secretions is less than 1% and include proteolytic enzymes, prostatic acid phosphatase and prostate-specific antigen. These are really important.
  • When the semen is first ejaculated it is lumpy, thick and viscous, this is to help deposit the sperm all in one place around the cervix and for it to remain there for a while making a reservoir around the cervix.
  • These enzymes then cause liquefaction of the semen making it more runny, this allows the sperm to swim up the cervical os.
    No liquefaction of semen indicates a problem with the prostate.
  • There is also high zinc concentration in the prostatic secretions (500-100x that of the blood), we believe these are anti-bacterial.
22
Q

Describe the normal values in a semen analysis

A

Semen volume: 1.5 – 6.0ml.
Sperm Concentration: 15 million/ml and above, below this is likely to be subfertility.
Liquefaction: Should occur in less than 30min.
Motility: Minimum sperm that should be motile is 40%, so 40%< is normal.
Progressive motility: Sperm moving in straight line, should be 32%

23
Q

Describe a sermatozoon (structure and function)

A
  • The mature sperm is stripped down and is the smallest cell in the body. It could be said to be similar to missile carrying its payload, the haploid DNA.
  • The oocyte is the largest cell in the body and contains all the machinery needed for cell division, the proteins, ribosomes, nutrients, enzymes etc. are in the egg. All our mitochondria is from the mother. All we get from the father is the haploid DNA.
  • The mitochondria in the spermatozoon is used to power the flagella to propel the sperm forward.
    The flagella has the structure, with columns running down which flip it from side to side.
  • Other ciliated structures e.g. in uterine tube and gut have same structure, with 9 pairs of fibres with two in the middle (every pair axoneme). They use ATP to slide against each other.
  • An important structure is the acrosome, this acts like a bag containing enzymes. As the sperm approaches the egg, the bag bursts and the enzymes cut through the outer layer of the egg.
24
Q

Can freshly ejaculated sperm fertilise an egg?

A

No, they have to undergo two processes. The first process takes 4-18 hours and involves changing the properties of the acrosome, this is called capacitation.
This is because we don’t want the sperm rushing in straight away and bursting against the uterus.