Spermatogenesis Flashcards
What is spermatogenesis?
The production of spermatozoa (mature male gametes) from spermatogonial stem cells
What are spermatozoa?
Mature male gametes
What are the main parts of the male reproductive system? (6)
- Testes
- Epididymis
- Vas deferens
- Seminal vesicle
- Prostate gland
- Urethra
What is the function of the testes? (2)
- Contains the seminiferous tubules of which the epithelium is the site of spermatogenesis
- Temperature is important for spermatogenesis and core body temperature is too high, hence why the testes are located outside
What is the function of the epididymis?
Sperm storage and maturation
What is the function of the vas deferens?
Transport of sperm from the epididymis to the urethra during ejaculation
What is the function of the seminal vesicle?
Produces a mucus secretion which aids the mobility of sperm
What is the function of the prostate gland?
Produces an alkaline secretion that neutralises the acidity of residual urine in the urethra and aids mobility of sperm
What is the function of the urethra?
Tube that carries urine and sperm out of the body
What are the 2 main functions of the testis?
- Produce androgens and other hormones for sexual differentiation and secondary sexual characteristics
- Produce spermatozoa for sexual reproduction which occurs in the seminiferous tubules with maturation occurring in the epididymis
What is the organisation of the testis? (2)
- Lobes of testis contains coiled up seminiferous tubules which are lined with seminiferous epithelium, location of Sertoli cells
- Separated by stroma containing blood vessels, lymph and Leydig cells
What is the function of the seminiferous epithelium? (3)
- Lines the seminiferous tubules
- Contains Sertoli cells
- Site of spermatogenesis
What are the 2 types of somatic supporting cells in the testes?
- Sertoli cells
- Leydig cells
What is the pathway of spermatogonial stem cell development to mature sperm? (6)
- Spermatogonial stem cells mature into spermatozoa in the seminiferous tubules
- Mature sperm are released into the lumen of the seminiferous tubules along with lots of fluid in spermiation
- Released into the rete testis, travel through the vasa efferentia
- 90% of fluid is absorbed in the vasa efferentia which is dependent on oestrogen
- Passage through the epididymis takes 5-11 days and sperm acquire ability to swim (and further maturation steps) which is dependent on androgens
- Mature sperm are stored in the tail end of the epididymis ready for ejaculation via the vas deferens
What are primordial germ cells (PGCs)? (3)
- Gamete precursors first identifiable in a foetus after 3 weeks gestation
- PGC population expands by mitosis and migrates to the genital ridge primordium by 6 weeks gestation
- The germinal epithelium also migrates in and will eventually become Sertoli cells (male) and Granulosa cells (female)
How does maternal drinking/drug taking impact the fertility of the offspring? (2)
- Number of Sertoli cells which migrate to the genital ridge primordium is determined at this point in gestation and is influenced by the microenvironment
- Maternal activity directly impacts the number of Sertoli cells present in the developing male foetus which affects their future sperm count
What is the function of the Sertoli and Leydig cells in the testes?
Support the developing germ cells and secrete sex steroid hormones
What are the steps of spermatogenesis? (5)
- Cell expansion of spermatogonial stem cells (diploid) via many rounds of mitosis
- Spermatogonium undergoes mitosis and produces a primary spermatocyte (diploid)
- Primary spermatocyte undergoes meiosis I and produces 2 secondary spermatocytes (haploid)
- 2 secondary spermatocytes undergo meiosis II and produce 4 haploid spermatids
- Final differentiation step to produce 4 genetically unique spermatozoa from spermatids is called spermiogenesis
How many sperm are made per day?
About 100 million starting at puberty
How do spermatogonial stem cells (SSCs) become primary spermatocytes? (5)
- The pool of SSCs undergo rounds of mitosis for self renewal
- The decision to self-renew or differentiate is determined by signals in the microenvironment i.e. growth factors
- At intervals, groups of morphologically distinct cells emerge: type A spermatogonia
- Type A spermatogonia undergo karyokinesis but not cytokinesis which produces a clone of 16 cells connected by cytoplasm which enter further rounds of mitosis with some differentiation in between
- This produces type B spermatogonia which go on to become primary spermatocytes
Where does spermatogenesis occur? (2)
- Seminiferous tubules
- Development occurs in a centripetal direction meaning as the sperm develop they migrate from the basement membrane into the lumen
What is spermiation? (2)
- Release of fully differentiated sperm into the lumen of the seminiferous tubule
- Not yet ready for fertilisation, fully differentiated but require further maturation steps
What are the main features of sperm morphology? (4)
- Acrosome cap over the head which develops from the Golgi apparatus and contains enzymes and proteins important for sperm-egg fusion in fertilisation
- Tail required for motility
- Mid-piece contains mitochondria (<10)
- Central axoneme made up of bundles of fibres
What is spermiogenesis? (5)
- Round spermatids undergo morphological changes to become mature spermatozoa
- Golgi apparatus forms the acrosome cap
- Nucleus changes shape to fit into the sperm head
- One of the centrioles of the spermatid elongates to become the tail
- Excess cytoplasm and organelles (residual body) are stripped off before spermiation and phagocytosed by Sertoli cells
What happens to chromatin when the nucleus is changing shape during spermiogenesis? (3)
- X and Y chromosome transcription stops before meiotic divisions
- Autosomal transcriptional activity stops later during spermiogenesis
- DNA is repackaged and histones are replaced by protamines resulting in tightly compressed chromatin with no gene expression
How do Sertoli cells support developing sperm? (4)
- Sertoli cells are in contact with germ cells of all different stages of development
- Sertoli cells span from the basement membrane to the lumen of the seminiferous tubules and adjacent cells are connected to each other via tight junctional complexes which forms the blood-testis barrier (BTB)
- Spermatogonia become spermatocytes once they enter meiosis and move away from the basement membrane
- Once spermatogonia cross into the adluminal compartment they are reliant on Sertoli cells for nutrients because of BTB
What is the blood-testis barrier (BTB)? (2)
- Tight junctions between Sertoli cells separate the the testes into basal and adluminal compartments
- Adluminal compartment is an ‘immune-privileged site’ which protects the haploid cells from immune attack
What is the duration of the spermatogenic cycle in man? (2)
- 64 days for completion of spermatogenesis
- At any given time there are 4 clones of developing sperm cells in each region of seminiferous tubule epithelium at different stages of maturation, a new clone is set off every 16 days (then each group take 64 days to become mature sperm)
How do Sertoli cells regulate spermatogenesis? (2)
- The wave of the seminiferous epithelium refers to communication between adjacent Sertoli cells via gap junctions and between Sertoli cells and developing germ cells
- This ensures that different sections of the tubule are are different stages of development to allow constant production of mature sperm
What was shown by Clouthier et al., 1996? (2)
- Rat SSCs transplanted into mouse seminiferous tubules developed as normal but imposed rat timing on spermatogenesis
- Shows that germ cells are playing a role in determining the timing as well as Sertoli cells (2 way communication)
How is spermatogenesis controlled hormonally? (6)
- Hypothalamus releases GnRH which causes the anterior pituitary to produce FSH and LH
- LH stimulates Leydig cells which produce testosterone, progesterone, oestrogens and oxytocin
- Lactotropes in the anterior pituitary are also stimulated by GnRH and produce prolactin
- FSH stimulates Sertoli cells which produce androgens, oestrogens, androgen binding proteins, activin and inhibin
- Inhibin also stimulates the Leydig cells and inhibin levels are indicative of sperm count
- Activin also stimulates the Sertoli cells and developing germ cells
What is the function of oestrogen in spermatogenesis?
Required for fluid absorption in the testis
What is the function of oxytocin in spermatogenesis?
Stimulates seminiferous tubule motility
What is the function of progesterone in spermatogenesis?
Supports spermiogenesis, capacitation and testosterone synthesis
What is the function of prolactin in spermatogenesis?
Enhances LH stimulation of Leydig cells
What hormonal feedback mechanisms are occurring during spermatogenesis? (3)
- Testosterone and progesterone negatively feedback onto the hypothalamus and anterior pituitary to reduce GnRH/LH/FSH production
- Negative feedback at the level of the hypothalamus is via KiSS1 neuron inhibition
- Activin activates the anterior pituitary (FSH production) and inhibin inhibits the anterior pituitary and antagonises activin
What is the function of androgen binding proteins in spermatogenesis?
Transport sex steroids to their place of action
What is the function of inhibin in spermatogenesis? (3)
- Negative feedback onto anterior pituitary to reduce FSH production
- Activin antagonist
- Stimulates Leydig cells and levels are indicative of sperm count
What is the function of activin in spermatogenesis? (3)
- Positive feedback onto anterior pituitary to stimulate FSH production
- Autocrine stimulation of Sertoli cells
- Paracrine stimulation of developing germ cells
How are steroid hormones converted in the testis? (4)
- Sex steroid hormones are connected by a biosynthetic network with cholesterol as the common precursor
- Some testosterone and androstenedione from Leydig cells enter the Sertoli cells
- They may be converted to the more potent dihydrotestosterone or to the oestrogens oestrone and oestradiol 17-beta
- These hormones act to stimulate the Sertoli cells but are also secreted into the blood or the tubular fluid
What is the role of testosterone in spermatogenesis? (5)
- Produced by Leydig cells and acts on Sertoli cells where it is essential for: maintenance of the blood-testis barrier, Sertoli-spermatid adhesion, spermatid elongation, spermiation, production of testicular fluid
- Converted within the Sertoli cells to dihydrotestosterone and oestrogen which further stimulate Sertoli cells and support spermatogenesis
- Essential for development of male secondary sex characteristics
- Travels to the seminiferous tubule lumen, binds to androgen binding proteins secreted by Sertoli cells, testosterone-ABP travels to and stimulates the ducts of the testes
- Autocrine negative feedback regulation on the Leydig cells
