Spermatogenesis

What are the 2 outcomes for the division of a spermatogonial stem cell?

• self renew

• commit to differentiation

What is the spermatogonial stem cell niche?

specialised physical and chemical environment

What causes spermatogonial stem cell self renewal?

paracrine signals from other cells in the niche

What are some examples of paracrine signals that cause a spermatogonial stem cell to self renew (3)?

• FGF2

• GDNF

• CXCL12

What is the essential signal for spermatogonial stem cell self renewal?

GDNF from peritubular myoid cells

What happens if spermatogonial self renewal fails?

run out of stem cells = spermatogenesis fails

What signal is required for spermatogonial differentiation when a spermatogonium divides?

retinoic acid

How does retinoic acid cause a cell to become committed to meiosis in a male (2)?

• acts as a ligand for nuclear transcription

• upregulates Stra8 = committed to meiosis

What vitamin is required for the formation of retinoic acid?

vitamin A

What type of hormone is retinoic acid?

steroid

What influences whether a spermatogonial stem cell differentiates or self renews?

position relative to niche - affects availability of mitogens

What is the name given to male germ cells undergoing meiosis?

spermatocytes

What are homologous chromosomes (3)?

• normal diploid (2n) cell

• 46 chromosomes in 23 pairs

• pairs are homologous - one maternal and one paternal

What phase of the cell cycle does DNA replication occur in?

interphase

What are sister chromatids (2)?

• replicated DNA

• each chromosome has 2 identical sister chromatids joined at the centromere

What does meiosis I result in (2)?

• homologous chromosomes (unique to meiosis)

• exchange of genetic information (in prophase I)

What does meiosis II result in?

separation of sister chromatids

What stage of spermatogenesis does meiosis I occur in in males?

primary spermatocytes

What stage of spermatogenesis does meiosis II occur in in males?

secondary spermatocytes

In which stage of meiosis does the change in ploidy occur (i.e. 2n → n)

meiosis I

What allows the movement of developing germ cells across the epithelium?

breaking and reforming of germ cell-sertoli cell adherens junctions

What type of junction forms the blood-testis barrier?

tight junctions between sertoli cells

Where do male germ cells move to after meiosis?

move past blood-testis barrier into immunologically privileged site - sertoli tight junctions ‘unzip’ to allow this

Why is the blood-testis barrier important?

helps avoid immune rejection of haploid cells

What happens to spermatogenesis when leydig cells are destroyed experimentally (4)?

• reduced testosterone

• gradual degeneration of spermatogenesis

• NO POST-MEIOTIC GERM CELLS

• androgens essential for progression through meiosis

What change occurs in post-meiotic germ cells?

morphological changes

What is spermiogenesis?

germ cell remodelling

What changes occur during spermiogenesis (4)?

• cytoplasm condenses

• acrosome and tail formation (polarisation)

• DNA compaction

• cytoplasmic storage of mRNAs required for future translation

What different parts of the spermatozoa are indicated by A-H (8)?

A. acrosomal vesicle

B. nucleus

C. midpiece

D. mitochondrion

E. plasma membrane

F. flagellum

G. tail

H. head

What does ‘A’ indicate on this diagram of a spermatozoa?

acrosomal vesicle

What does ‘B’ indicate on this diagram of a spermatozoa?

nucleus

What does ‘D’ indicate on this diagram of a spermatozoa?

mitochondrion

What does ‘F’ indicate on this diagram of a spermatozoa?

flagellum

What are the 4 phases of spermiogenesis?

• golgi phase

• cap phase

• acrosomal phase

• maturation phase

What happens during the golgi phase of spermiogenesis (3)?

• round cell becomes polar

• golgi → head end

• centrioles → tail end

What happens during the cap phase of spermiogenesis (2)?

• acrosomal vesicle forms cap over nucleus

• primitive flagellum forms

What happens during the acrosomal phase of spermiogenesis?

acrosome begins to spread around nucleus

What happens during the maturation phase of spermiogenesis (2)?

• mitochondria gather in midpiece

• excess cytoplasm is lost as residual body

What stage of spermiogenesis is shown in this image?

golgi phase (1st phase)

What stage of spermiogenesis is shown in this image?

cap phase (2nd phase)

What stage of spermiogenesis is shown in this image?

acrosomal phase (3rd phase)

What stage of spermiogenesis is shown in this image?

maturation phase (4th phase)

What happens to residual bodies produced in the maturation phase of spermiogenesis?

phagocytosed by sertoli cells

How is DNA packaged into sperm (4)?

• replacement of somatic histones with specialised histones

• transcription stops

• histones replaced with transition proteins

• transition proteins replaced with protamines

What shape is DNA packaged into in somatic cells and why?

solenoid - DNA remains accessible for cellular processes

What shape is DNA packaged into in sperm and why?

annulus - tighter packed than somatic cells as does not need to be accessed

What % of histones are replaced with protamine when DNA is packaged into sperm?

85%

When does transcription stop during spermatogenesis?

early spermatid nucleus

What is spermiation?

spermatozoa release from sertoli cells

What happens during spermiation (3)?

• sertoli-germ cell junctions undergo extensive remodelling

• sperm released

• leave behind residual body that is phagocytosed by sertoli cell

Where are specific germ cell stages found?

grouped together in seminiferous epithelium

How are the different germ cell stages arranged in male rodents in the seminiferous tubule?

segmental arrangement

How are the different germ cell stages arranged in male humans in the seminiferous tubule?

helical arrangement

Why are there different stages of germ cell development in the same seminiferous tubule (3)?

• allows continual release

• not all sections of tubule releasing spermatozoa at same time

• prevents periods of infertility

How long does human spermatogenesis take?

64 days

How long does mouse spermatogenesis take?

35 days

Why are different parts of the seminiferous tubule at different stages of germ cell development? What causes this? (3)

• spatial availability of retinoic acid

• need retinoic acid available to start at stage 1

• availability controlled by coordination of other cells in the niche

Why are different stages of spermatogenesis grouped together (2)?

• different stages in different cells take the same amount of time as each other

• e.g. all the blue arrows take the same amount of time as each other, all the red take the same amount of time etc…