L9: Spermatogenesis Flashcards

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1
Q

What are the key phases in spermatogenesis?

A
  • Proliferation of spermatogonia (one spermatogonium –> many spermatozoa)
  • Generation of genetic diversity by meiosis (Diploid spermatogonia –> haploid, genetically diverse spermatozoa) – beneficial because introduces genetic diversity to offspring
  • spermiogenesis (round spermatogonia –> tadpole-shaped spermatozoa)
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2
Q

Describe differences between spermatogonia, spermatocytes, spermatids, spermatozoan

A
  • spermatogonium – diploid stem cells
  • spermatocytes – spermatogonium after mitosis
  • Spermatids – spermatocytes at meiosis divide into 4 haploid spermatids
  • Spermatozoan – differentiated spermatid
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3
Q

Where does spermatogenesis take place?

A

Spermatogenesis proceeds from the basal to luminal surface of the seminiferous epithelium

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4
Q

Describe spermatogenesis including key processes and names of the cells at different stages

A

spermatogonium (diploid stem cell) undergoes mitosis providing cell numbers essential for a high sperm output.
While undergoing meiosis they become spermatocytes, and after meiosis, each spermatocyte divides into 4 haploid spermatids.
After that differentiation takes place (morphological changes) and when released spermatids become spermatozoan.

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5
Q

What is the purpose of spermatogonial mitosis? what are the experimental evidence?

A

Provides lots of cells for meiosis (experimental evidence: PCNA staining marks cells undergoing mitosis in testis)

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6
Q

What are the two paths for spermatogonial stem cells?

A

They can either self-renew or commit to differentiation.

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7
Q

What are the types of undifferentiated spermatogonia in humans? What is their function?

A
  • Ad (Adark) (renew population)
  • Ap (Apale) (provide population for spermatogenesis)
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8
Q

What are the types of differentiating spermatogonia in humans?

A

B, cannot go back once commited.

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9
Q

What are the types of undifferentiated and differentiating spermatogonia in rodents and chimps?

A
  • In non-human primates similar patterns are seen, they also have Ad and Ap. However, they have more divisions after the spermatogonia entered the differentiation state (B1->B2->B3->B4)
  • In rodents (slightly different): Undifferentiated spermatogonia can be Asingle (As), they can self-renew or become Apaired (Apr), continue dividing until they form Aal spermatogonia, form syncytia which are attached together in 4, 8 or 16 cells. Then enter differentiating spermatogonia stage (A1->A2->A3->A4->In->B)
  • Key message: undifferentiated spermatogonia keep dividing and can always self-renew, replenish the pool, however when they commit to differentiating spermatogonia, they cannot go back.
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10
Q

What is spermatogonial stem cell niche? What makes it up?

A
  • The spermatogonial stem cell niche is a specialised physical and chemical environment (formed by surrounding cells).
  • Made up from: sertoli cells, PTM cells, Leydig cells, blood vessels, lymphatics, differentiated spermatogonia.
  • Dividing SSCs can receive signals from all through the testis and through the body, which come from the blood vessels. Physical contact with basement membrane is also essential for signalling

SEE L9, slide 7

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11
Q

What are the ligands that SSCs require for self-renewal?

A

Paracrine signalling, main ligands FGF2, GDNF, CXCL12, ensures that stem cells still divide

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12
Q

What produces GDNF?

A

GDNF is produced by peritubular myoid cells

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13
Q

What is a key ligand for spermatogonial differentiation?

A

Retinoic acid, produced from retinol or vitamin A, that’s why vitamin A essential in our diet

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14
Q

When is retinoic acid released?

A

Not until after puberty

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15
Q

What is the genomic pathway that retinoic acid acts through?

A

RA acts on transcription factor, which causes expression (upregulation) of Stra8, promote start of meiosis

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16
Q

What is the non-genomic pathway that retinoic acid acts through?

A

Results in translation of KIT through mTOR pathway, promote start of meiosis

17
Q

What determines whether spermatogonium differentiates or self-renews?

A

The position of a spermatogonium relative to the niche affects the availability of mitogens and therefore whether it differentiates or self-renews

18
Q

What are the male germ cells undergoing meiosis called?

A

Spermatocytes (large nuclei, can see condensed chromosomes)

19
Q

How many chromosomes does a normal human cell have?

A

46

20
Q

What are homologous chromosomes?

A

46 choromosomes make up 23 pairs of homologous chromosomes, one of each is from the mother or one from the father. Most human cells are diploid because there are two chromosomes in a homologous pair

21
Q

What are sister chromatids?

A

Just before entering meiosis or mitosis, a cell replicates its DNA in interphase, each chromosome now consists of two identical sister chromatids joined at the centromere

22
Q

What is the result of meiosis I?

A

Meiosis I involves separation of homologous chromosomes (2n –> n) and exchange of genetic information (diverse offspring)

Slow because of crossingover (homologous recombination), genetic info exchange. Crossingover occurs during prophase I (during pachytene phase of prophase I homologous recombination occurs)

23
Q

What is the result of meiosis II?

A

Meiosis II results in the separation of sister chromatids (n –> n)

24
Q

How does a germ cell attach and move from basal to luminal side of seminiferous tubules?

A
  • Germ-Sertoli cell adherens junctions are broken and reformed as the cells move across the epithelium.
  • Sertoli-Sertoli tight junctions are specialised to form the blood-testis barrier (immunologically privileged)
  • Unzips at meiosis to allow spermatocyte transit
25
Q

How is the blood-testis barrier important? Where is it formed?

A

Avoiding immune rejection of haploid cells. It forms between the transformation of spermatocytes from diploid to haploid cells, thus haploid cells can’t be attacked

26
Q

What is essential for progression through meiosis?

A

Androgens, destruction of Leydig cells using ethane dimethane sulphonate causes reduction in interstitial testosterone.
Reduction in testosterone causes gradual degeneration of spermatogenesis
NO post-meiotic germ cells

27
Q

What is spermiogenesis?

A

Morphological changes in post-meiotic germ cells

28
Q

What are the morphological changes during spermiogenesis?

A
  • condensation of cytoplasm
  • formation of acrosome and tail (defines polarity)
  • DNA compaction
  • Cytoplasmic storage of mRNAs required for future translation
29
Q

What is the order of phases of spermiogenesis?

A
  1. Golgi phase
  2. cap phase
  3. acrosomal phase
  4. maturation phase
30
Q

What happens during Golgi phase?

A

Round cell becomes polar, Golgi = head end, centrioles = tail end

31
Q

What happens during cap phase?

A

acrosomal vesicles forms cap over nucleus, primitive flagellum forms (can’t move)

32
Q

What happens during acrosomal phase?

A

acrosome begins to spread around nucleus, midpiece starts to form

33
Q

What happens during maturation phase?

A

Mitochondria gather in midpiece, excess cytoplasm lost as residual body

34
Q

What is the difference between DNA packaging in somatic cells and in sperm?

A
  • Somatic histones are replaced with specialized histones called protamines
  • Which stops transcription, compacted in annulus
  • Transcription stops in the early spermatic nucleus
35
Q

What is spermiation?

A

Process of spermatozoa release from the Sertoli cell.
- sertoli-germ cell junctions undergo extensive remodelling
- when sperm are released they leave behind a ‘residual body’ of cytoplasm
- this is phagocytosed by the Sertoli cell

36
Q

How many germ cell stages are there in mouse testis?

A

Specific germ cell stages are found grouped together in the seminiferous epithelium, in mouse there are totally 12 stages at which sperm can be found at different phases of development.

37
Q

What is the difference in the arrangement of germ cell stages between rodents and humans? Why is it important?

A

Rats have segmental arrangement of stages, while humans have helical/twisted arrangement of stages.
It is important so not all sections of the seminiferous tubule are releasing spermatozoa at the same time, because then males would only be fertile only at certain points.

38
Q

How are these arrangements of germ cells controlled?

A

Spermatogenic ‘wave’ is controlled by pulses of retinoic acid?
Retinoic acid causes spermatogonial differentiation (Aal –> A1)
This always occurs at stage VII –> VIII of the spermatogenic cycle in mice, just as spermiogenesis is occuring