Spermatogenesis Flashcards
1
Q
How is sperm produced and released?
A
- Produced in the testes and stored in the epididymis
- During ejaculation, contractions in the epididymis and vas deferens propel the sperm up and out through the vas deferens. Sperm is mixed with epididymal fluid at this stage.
- Sperm + epididymal fluid reach seminal vesicles from the two vas deferens.
- Sperm + epididymal fluid + secretions from seminal vesicles.
- As it approaches the ejaculatory duct, secretions from the prostate and Cowper’s glands (just underneath the prostate) are added.
- Ready for ejaculation. The corpus cavernosum is normally filled with blood when there is an erection. The corpus spongiosum (tissue underneath) remains flexible, while the corpus cavernosum is filled with blood. The importance of this is to keep the urethra open to allow for the passage of semen.
2
Q
What is the evolutionary significance of testes hanging outside the body?
A
- Testes produce sperm and store it
- Normal volume of about 15-25ml
- Testes produce hormones, particularly testosterone, which regulate spermatogenesis
- Testes lie in scrotum outside of body cavity; well-vascularised, well-innervated, 1.5-2.5 degrees below body temperature (optimum temperature for sperm production)
- After ejaculation into the female tract, it is possible the temperature difference acts as a form of sperm activation.
3
Q
What is the structure of a testicle?
A
- Seminiferous tubules-rete testis-epididymis-vas deferens
- About 300 lobes filled with seminiferous tubules in the average testis
- Tightly coiled tubules collect in rete testis
- Efferent ductules lead to epididymis
- Epididymis is a highly convoluted, tubular structure made of three segments = head, body, tail (caput, corpus, cauda)
- 90% of the testes is actually seminiferous tubules (about 600m)
4
Q
What happens at the seminiferous epithelium of the seminiferous tubules?
A
- Mitotic division of primordial germ cells allows males to have a lifetime supply of sperm cells, unlike females born with a fixed number of primordial oocytes.
- Adluminal compartments are tight junctions between each sertoli cell. Area where sperm develop.
- The seminiferous epithelium has a basal membrane (basal lamina).
- Spermatogenic (germ) cells can be seen undergoing spermatogenesis with different cell divisions taking place. Released into lumen.
5
Q
What is the role of the sertoli cell?
A
- Maintain close contact with the sperm and mediate between the endocrine system and the developing sperm, receiving signals and severing factors that help sperm to develop (+feedback)
- Between each cluster of germ cells, there are Sertoli cells. They respond to testosterone and regulate the process of spermatogenesis (the divisions that are taking place). Just outside of the basal lamina, the leydig cells can be seen. The leydig cells produce testosterone. The testosterone crosses the basal membrane to the Sertoli cells. The Sertoli cells respond to this and use it to regulate spermatogenesis.
- Germ cell-primary spermatocyte (diploid)-secondary spermatocyte (haploid)-spermatids-spermatozoa
- From primary spermatocyte (type B spermatogonia more specifically), the germ cell is committed to meiosis (no going back)
6
Q
What is the purpose of tight junctions?
A
- Exist between Sertoli cells to form the blood-testis barrier.
- Open to allow passage of spermatogonia prior to completion of meiosis. The germ cells dividing are forcing their way through those junctions and dividing through them. The junctions form a seal around each of the germ cells. This is important as the surrounds are well-vascularised (blood-testis barrier)
- Important to note that two compartments are formed as a result of the tight junctions = divides into basal and adluminal compartments
- Protects spermatogonia from immune attack
- Allows specific enclosed environment for spermatogenesis which is filled with secretions from Sertoli cells. Sertoli cells provide sustenance for the spermatogenic cells. This regulatory process takes place via the formation of tight junctions.
7
Q
Why is it important for tight junctions to form a blood-testis barrier?
A
- The tight junctions creates a seal that forms the blood-testis barrier which separates the testis from the blood (and immune system). This protects the germ cells from immune attack.
- If the testes (or spermatogenic cells) were exposed, the immune system would create antibodies against the spermatic and attack the germ cells. These antibodies would agglutinate on the sperm and slow them down, preventing them from functioning normally. The classic case is a vasectomy reversal; when the vas deference has been reattached and is healing, there is sometimes leakage of sperm into the system and anti-sperm antibodies are developed as a result.
- The surroundings are well-vascularised (lots of capillaries outside of the basal lamina), so tight junctions are important to protect the spermatogenic cells.
8
Q
What are the stages of spermatogenesis?
A
1) Spermatagonia
- Germ cell on basement membrane
- Diploid
- Capable of mitotic divisions to produce more spermatogonia or meiotic divisions to produce primary spermatocytes
- Two populations = type A amd type B. Two categories of type A = type A dark and type A pale. Type A dark can either give rise to another copy of itself or could differentiate into a type A pale. Type A pale undergoes further differentiation into type B spermatogonia. At this point, it is committed to the differentiated pathway for spermatogenesis. The type B then undergoes further differentiation into primary spermatocytes
2) Primary spermatocytes
- Cell committed to differentiative pathway
- Diploid
- Move into adluminal compartment and duplicate DNA to produce sister chromatids which exchange genetic material and enter meiosis I.
- Following the first meiotic division, two daughter cells are formed with haploid number of chromosomes that are arranged as sister chromatids. These are called secondary spermatocytes.
3) Secondary spermatocytes
- Have undergone meiosis I
- Haploid number of chromosomes arranged as sister chromatids
- Undergo second meiotic division
4) Spermatids
- Meiosis II produces four truly haploid spermatids (round in shape)
- Marks the end of mitotic and meiotic divisions associated with spermatogenesis
- Differentiations that confer maturity take place after (maturation).
- Extra cytoplasm removed, formation of an acrosome and tail. Condensation of spermatogenesis nuclear chromatin characterised by the replacement of spermatogonial histones with sperm-specific protamines results in transcriptional inactivity in spermatozoa.
- Maturation process is known as spermiogenesis; transforms round spermatids to complex spermatozoa
5) Spermatozoa
- New cycle every 16 days, entire process takes approximately 74 days.
- Movement into lumen is controlled by Sertoli cell secretions. Factors produced by Sertoli cells are required for development.
To summarise:
1) Mitotic proliferation of spermatogonia
2) Meiosis and development of spermatocytes
2) Spermiogenesis = elongation, loss of cytoplasm, movement of cellular contents
9
Q
Summarise the HPG axis
A
- In the archetypal HPG axis paradigm, there is a positive drive of GnRH from the hypothalamus to the pituitary (pulsatile release)
- Differs between males and females (cyclical in females. Once FSH and LH act on the ovaries in females, oestrogen and progesterone can act negatively in terms of feedback on the hypothalamus and pituitary. When the oestrogen threshold is exceeded in the case of ovulation, positive feedback acts on the hypothalamus and anterior pituitary.
- In the case of males, there is always a tonic level of hormone production (not cyclical, fairly constant) and the feedback is always negative.
- The androgens and inhibit always feedback negatively on the HPG axis.
10
Q
Where do LH and FSH act in the testes?
A
- LH from the anterior pituitary acts on LH receptors found on leydig cells.
- Leydig cells convert cholesterol into androgens.
- Intratesticular testosterone levels are 100x those in plasma.
- Androgens produced by leydig cells cross over to stimulate Sertoli cell function and thereby control spermatogenesis.
- Sertoli cells contain FSH receptors and convert androgens to oestrogen.
- FSH established a quantitatively normal Sertoli cell population, whereas androgen initiated and maintains sperm production. FSH acts directly on Sertoli cells to regulate numbers. Also provides sustenance to growing germ cells. Produced androgen-binding protein. The ABP binds to testosterone and then concentrates this testosterone within the seminiferous epithelium to aid with regulation of spermatogenesis.
11
Q
How does inhibin act in the testis?
A
- Inhibin B is produced in males by Sertoli cells in response to FSH
- Reduces FSH production by the anterior pituitary
- Germ cells appear to be required for Inhibin B production
- FSH and Inhibin B in combination have been correlated with testicular volume and spermatogenic activity but this hasn’t been proven clinically useful as yet (thought it would have the same clinical value as AMH which is a good indicator of ovarian reserve; thought it would be the male version, inhibin + activin + AMH all have very similar structures). Semen analysis remains the gold standard for assessing male fertility.
12
Q
Describe the structure of the spermatozoon.
A
- Cytoskeletal structure can be divided into two main regions = head and flagellum (tail)
- Tail can be further divided into three distinct regions = middle piece, principal piece and end piece
- Head contains a nucleus and acrosomal region
- Middle piece contains mitochondria (for energy£) and houses a lot of ion channels (responsible for intercellular calcium signalling in the sperm when it is in the female reproductive tract in response to extracellular signals)
- Head (5 micrometers)-neck-middle piece (5 micrometers)-principal piece (50 micrometers)-endpiece (5 micrometers)
13
Q
Describe the ejaculate.
A
- 300 million spermatocytes produced per day on average
- Normal ejaculate volume is 1.5 - 6 ml (WHO criteria)
- Spermatozoa account for very small proportion of the total volume of the ejaculate (1 - 5%)
- Initial portion of the ejaculate is the most sperm rich. 99.9% lost before reaching the ampulla of the uterine tube. Around 120,000 sperm get close to the egg, only one penetrates.
- Seminal fluid consists of secretions from = seminal vesicles, prostate, bulbo-urethral (Cowper’s) gland combined with epididymal fluid
14
Q
What is the role of the seminal fluid?
A
- Transport of sperm through the male reproductive tract and through the female reproductive tract. When in the male reproductive tract, the sperm itself is non-motile.
- Coagulation of the ejaculate and creating a sperm deposit in the vagina. When initially ejaculated, it is in the form of a coagulant which liquifies later on. This coagulative deposit gives the sperm a better chance of making its way through the cervix and into the female reproductive tract (would just leak out of the vagina if it was all liquid to begin with).
- Creates a neutral to slightly alkaline bugger milieu in the vagina to protect spermatozoa from the acidic vaginal milieu.
- Activation and augmenting the motility of the sperm cells. Once the sperm comes into contact with ejaculated seminal fluid, motility is activated.
- Coating the sperm cells with capacitation inhibitors. Capacitation is the process that sperm cells have to go through in order to be able to fertilise an egg. If capacitation takes place before it makes its way past the cervix, it would have occurred too early (needs to occur when it is just arriving/on its way to the egg).
- Applying nutrients for the sperm cells
15
Q
Draw parallels between the meiotic and mitotic aspects of spermatogenesis and the fundamental mitosis and meiosis divisions.
A
To be answered
