2 - Spermatogenesis Flashcards by Maxim Wallace

What are the accessory glands of the male reproductive tract?

Seminal vesicles
Prostate
Bulbo-urethral gland

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What muscle maintains testis temperature within a narrow range?

Cremaster muscle

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What is the general function the testis?

Site of sperm production

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What is the function of the epididymus?

Sperm collection / maturation

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What is the function of the vas deferens?

Sperm transport

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What is the overall function of the accessory glands?

Contribute to seminal fluid

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What is the function of the urethra?

Transport

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What is the path of a sperm through its development along the male reproductive tract (in the testicle)?

Seminiferous tubules
Rete testis
Ductus efferentes
Epididymus

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What do sperm first acquire motility?

Epididymus

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What hormone enables sperm motility within the epididymus?

DHT

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What enzyme mediates the conversion of DHT from testosterone?

5alpha-reductase

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Why is the sperm fraction concentrated within the epididymus?

Capable of reabsorbing fluid within the epididymus.

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What proteins are secreted within the epididymus to arrest sperm function?

Proteins that bind to sperm head and inhibit EARLY capacitation.

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What is the function of Leydig cells?

Where are they found?

Leydig cells convert cholesterol into testosterone.

Around the seminiferous tubules.

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Where is testosterone converted into DHT?

Sertoli cells

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What 2 cell populations make up the seminiferous epithelium?

Sertoli cells

Spermatogenic lineage cells (sperm precursors)

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Outside the seminiferous tubules, what two cells are found?

1) Leydig cells

2) Myoid cells

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What are the 2 functions of myoid cells?

Structural integrity.

Movement of sperm.

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What are the 2 important compartments of the seminiferous tubules?

1) Adluminal compartment

2) Basal compartment

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What characteristics / functions of both the adluminal / basal compartments are different?

Adluminal membrane = diffusional barrier.

Basal layer = barrier to blood supply.

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Why is the structural integrity of the basal layer so important?

Stops contact of sperm and blood.

Inhibits possibility of big auto-immune reaction.

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What is the name of an immune reaction if sperm were to enter the blood stream?

Autoimmune orchitis.

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How many mature sperm can a single spermatogonium make?

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In the progression of 1 spermatogonium, how many rounds of mitosis occur?

What is this process termed as?

Clonal expansion

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Following 4 rounds of mitosis, what process then occurs? At what stage of sperm development?

Meiosis I and II Spermatocyte

What are the two distinct phases of spermatogenesis?

Spermatocytogenesis Spermiogenesis

Following meiosis, what stage of sperm production is reached?

Spermatid

In the context of genetic information, how is the spermatid different from its precursor?

Haploid

What is the final stage of spermatogenesis?

Spermiogenesis

What is spermiogenesis?

Cytoplasmic remodelling of the sperm. Final stage, seeing the maturation of spermatids into spermatozoa.

In spermiogenesis, what do golgi eventually form?

Lysosomal granules which coalesce to form the acrosome.

What do the proximal centrioles form in spermiogenesis?

Neck of sperm

What do the distal centrioles form in spermiogenesis?

Flagellum

What do the mitochondria form in spermiogenesis?

Flagellar motor

What is the function of cytoplasmic droplets?

Remove excess cytoplasm

What is the process called when sperm are released into seminiferous tubule lumen?

Spermiation

What enzymes are contained within the acrosome?

Hyaluronidases

What cells do hyaluronidase enzymes mainly digest?

Cumulus cells

How is DNA packed within the head of the sperm? Why is this?

Histone proteins are exchanged for smaller, protanine proteins. Too large for sperm head space.

What is the DNA within the head of the sperm known as?

Heterochromatin | tightly packaged DNA

What gene is really important in ensuring the integrity of sperm head structure?

DPY19L2 Gene that codes for a protein which anchors the nuclear membrane to the acrosomal cap.

How are mitochondria arranged, relative to the flagella?

Arranged helicoidally around the flagellum.

What arrangement of microtubules occurs in the sperm mid-piece?

9*2 +2 arrangement. 9 doublets in a circle with a single central doublet.

What are the 3 regions of the mature sperm?

Head Midpiece Principle piece

What region of the sperm contains the mitochondria?

Midpiece

Microtubules are associated with an important protein. What is it? What is its function?

Dynein. ATP-ase. Provides microtubules with energy by hydrolysing ATP.

How many spermatocytes do spermatogonium give rise to?

How many spermatozoa to do primary spermatocytes give rise to?

How many spermatagonia start the process of sperm development EACH DAY?

3,000,000

How many die each day?

Half of 3 million

How many sperm are left each day?

10^8.

How long does sperm formation take?

70 days

How many days does it take sperm to reach the ejaculatory ducts from being formed?

14 days.

What 4 components make up the normal sperm fraction?

1) Epididymus + vas deferens 2) Prostate 3) Seminal vesicle 4) Bulbourethral gland

What percentage does the epididymus + vas deferens contribute to the ejaculate volume?

5% | sperm-rich

What % does the prostate contribute to the ejaculate volume?

13-33%

What % does the seminal vesicle contribute to the ejaculate volume? What two components are important in this secretion?

45-80% Prostaglandins Fructose (ENERGY)

What % does the bulbourethral gland contribute to the ejaculate volume?

What pattern of sperm motility occurs when semen meets cervical mucus?

Arrange themselves into columns (groups of sperm) known as phalanges.

What hormonal changes in the female mediate the viscosity of cervical mucus?

Estrogen predominating results in mucin production, making the mucus less viscous - arranges proteins into channels. Progesterone then inhibits estrogen production and mucus becomes impenetrable.

What % of males are infertile?

5-7%

What fraction of couples are infertile?

1/6

What are some of the major causes of male infertility?

Sperm production (i.e. low numbers, poor quality)

What fraction of infertile couples are thought to to be solely due to male issues?

Over 1/3

Give examples of infertility causes:

Varicocele Infection Ejaculatory problems Hormone imbalance Lifestyle

What does the term 'Globozoospermia' refer to ?

Production of round-headed sperm.

What is the pathophysiology of globozoospermia?

Undeveloped acrosome cap.

The mutation of which gene can result in globozoospermia?

DYP19L2

What is the inheritance pattern in a mutated DYP19L2 gene?

Autosomal recessive

What is a general overview of the procedure that occurs in Intracytoplasmic Sperm injection (ICSI) ?

Similar procedure to IVF where both egg and sperm are removed from respective partners. ICSI artificially implants sperm into oocyte in cases where sperm are incapable of doing so.

What are 6 clinical findings shown through ICSI in rodent studies?

1) Decreased rate of preimplantation embryonic development. 2) Decreased offspring number 3) Higher post-natal weight grain 4) Increased tumour formation rate 5) Increased anxiety in female offspring 6) Premature ageing

What is the principle behind germline stem cell research for spermatogenesis?

Spermatogonial stem cells can be isolated from testis tissue. Cryopreserved. Transplanted back into recipient when reached sexual maturity. Potentially become capable of sperm production.

What clinical condition might germline stem cell therapy be useful?

In children with leukaemia - require high dose chemotherapy / irradiation which can render them infertile.

Why might constant economic growth be at the root of poor sperm quality? (Author?)

Low demand for big families. Almost no selective pressure. Selecting for sperm that aren't optimal. (Lutz W,. 2006)

Name one example of a genetic disease that, without modern reproductive techniques, would render an individual infertile, but would now not?

Klinefelter's syndrome. Would be 47XXY (Klinefelter's), traditionally thought to be infertile. However, testis biospy or recovery from ejaculate would find samples of 23X 23Y sperm. HOWEVER, might HIGHER RATES OF ANEUPLOIDY.

What is an important difference often found amongst infertile sperm compared to fertile samples in the context of resistance to oxidative stress?

Naturally, with very small cytoplasmic space, sperm are predisposed to oxidative stress as a result of having few anti-oxidative enzymes. Also a large number of oxidative attack sites in light of many POLYUNSATURATED fatty acids.

What is the differences, in the context of oxidative stress, between normal DNA and sperm DNA (heterochromatin)?

Heterochromatin is much more resistant to oxidative attack - protamines? However, heterochromatin is much less capable of DNA repair.

There are only two known heterochromatin repair enzymes. What are they?

OGG1 APE1

What is commonly found, in the context of oxidative stress, in sub-fertile individuals?

Oxidative attack as a result of relative lack of DNA repair capital.

Although men can continue to make sperm beyond 80, what factor of oxidative damage is true for males over 35 years old, compared to younger counterparts?

3x the amount of oxidative damage.