Lecture 10: Spermatogenesis Flashcards
Male reproductive anatomy
Process of ejaculation
1 - Contraction in epidydemis & vas defers -> propels sperm (& epididymal fluid)up and out through vas deferens
2- This fluid travels through vas deferens; at seminal vesicle, seminal vesicle fluid added.
3- At ejaculatory duct, secretions from prostate & Cowper’s gland added
4- fluid ejected
What makes up ejaculatory fluid?
- Sperm
- Epididymal fluid
- Seminal vesicle secretions
- Prostate secretions
- Cowper’s gland secretions
Characteristics & function of testes
- Produce sperm and store it.
- Produce hormones (T) which regulate spermatogenesis.
- Lie in scrotum outside body cavity
- Well-vascularised, well-innervated.
- Normal volume of testes approximately 15-25ml.
How can the volume of testes be measured?
- Orchidometer
What will happen if testes overheat?
- Reduced sperm count
What is the optimum temperature for sperm production
- 1.5-2.5C below body temp. (approx. 35C)
Is there an evolutionary benefit to testes laying outside body cavity?
- School of thought which believes there is a benefit.
- Ejaculation of sperm into vagina -> activation of sperm to fertilise
Testicular anatomical structure and through which structures do sperm travel?
Seminiferous tubules -> rete testis -> epididymis -> vas deferens
What is the testis 90% made up of?
- Seminiferous tubules
(600m ST in each testis- tubules are tightly coiled)
Approx how many lobes filled with seminiferous tubules in one testis?
300
Seminiferous epithelium structure
- brown outer lining = basal lamina/membrane
Process of spermatogenesis
What is the function of Sertoli cells in the seminiferous epithelium?
- Respond to T
- Function to regulate the process of spermatogenesis
- Provide sustenance for spermatogenic cells
Where do we find tight junctions in the male gonad?
- Seminiferous epithelium
What are the characteristics and function of tight junctions?
- Exist between Sertoli cells forming blood-testis barrier.
- Open to allow passage of spermatogonia prior to completion of meiosis.
- Divides into basal and adluminal compartments.
- Protects the spermatogonia from immune attack.
- Allows specific enclosed environment for spermatogenesis which is filled with secretions from Sertoli cells.
How is spermatogenesis regulated in the testes?
Leydig cells -> produce T -> T passes Basal L. to Sertoli cells -> S. cells respond to T = regulate spermatogenesis
How is spermatogenesis regulated in the testes?
Leydig cells -> produce T -> T passes Basal L. to Sertoli cells -> S. cells respond to T = regulate spermatogenesis
What is the importance of the blood-testis barrier created by the tight junctions? And what may happen during a vasectomy reversal failure?
- Prevents AB production against spermatogenic/germ cells
- Protects spermatogenic cells from a lot of toxins – most toxins cannot pass through the blood-testis barrier
- vasectomy reversal procedure -> vas deferrers reattached -> may lead to sperm leaking out healing vas deferens, passing barrier & entering blood system -> anti-sperm ABs produced
What are the names of the different stages of spermatogenesis?
- Spermatogonia
-> Primary spermatocyte
-> Secondary spermatocytes
-> Spermatids
=> Spermatozoa
Describe spermatogonia
- Germ cell on basement membrane,
- Capable of mitotic or meiotic division to produce primary spermatocytes or more spermatogonia by mitosis.
- They are diploid.
Describe primary spermatocyte
- Cell committed to differentiative pathway,
- 46XY diploid.
- They move into the adluminal compartment
- duplicate their DNA to produce sister chromatids which exchange genetic material & enter meiosis I.
Describe secondary spermatocytes
- Undergone meiosis I
= 23X + 23Y haploid number of chromosomes (arranged as sister chromatids).
Describe spermatids
- Meiosis II occurs to give 4 haploid spermatids.
- Round spermatid -> elongated spermatid differentiation.
Describe spermatozoa
- Mature sperm extruded into the lumen
What is spermiogenesis?
- Spermatids differentiate into mature spermatozoa
- Removal of extra cytoplasm & tail
- Acrosome formation
- condensation of sperm nuclear chromatin characterised by the replacement of spermatogonial histones with sperm-specific protamines. This results in transcriptional inactivity in spermatozoa.
What is the difference between Ad, Ap and B?
Ad: can copy itself & differentiate into Ap
Ap: undergoes further differentiation into spermatogonia
B: At this point, the cells are committed to differentiated pathway for spermatogenesis
What does meiosis I arise and what does meiosis II arise?
MI: Secondary spermatocytes
MII: Spermatids
What does spermiogenesis produce?
- Spermatozoa
Why do men always have a supply of spermatogonia?
- Due to dark spermatogonia
- diploid
- undergo mitotic divisions
Summarise spermatogenesis (process & length of time) & what is the importance of Sertoli cells?
- Mitotic proliferation of spermatogonia.
- Meiosis and development of spermatocytes.
- Spermiogenesis, elongation, loss of cytoplasm, movement of cellular contents.
- Movement into lumen controlled by Sertoli cell secretions.
- Factors produced by sertoli cells are required for development.
- New cycle every 16 days, entire process takes approximately 74 days.
HPO vs HPT axis
How is testosterone produced in the testes?/ function of LH in spermatogenesis
A. pituitary -> LH -> LHR on Leydig cells -> conversion of cholesterol to T in Leydig cells -> cross over to and stimulate Sertoli cell function
= initiation, maintenance & regulation of spermatogenesis
What does FSH do and its function in spermatogenesis?
A.pituitary -> FSH -> FSHR on Sertoli cells -> conversion of androgens to E2
Function:
- regulation of Sertoli cell population;
- allows Sertoli cells to act on their sustentacular role;
- PRODUCTION OF ABP -> binds to T = concentrates T in epithelium
Significance of inhibin in spermatogenesis
- InhibinB is produced primarily by Sertoli cells in response to FSH
- Inhibin B reduces FSH production by the anterior pituitary (negative feedback).
- Germ cells appear to be required for Inhibin B production.
- FSH & Inhibin B in combination have been correlated with testicular volume & spermatogenic activity but this hasn’t proved clinically useful as yet.
How to test for male fertility?
- Semen analysis
Spermatozoon ~5uM structure
How many sperm produced per day on average and how many ejaculated?
- 300 million
- approximately 120 million in average ejaculate
What is the normal ejaculate volume?
- 1.4ml - 6ml
How much of the ejaculate volume contain spermatozoa?
- 1-5%
Where is sperm most rich in the ejaculate?
Initial portion of the ejaculate
What is the amount of sperm present at each section of the female reproductive tract?
- 99.9% lost before reaching ampulla of the uterine tube
- around 120,000 sperm get near to egg,
- only one enters
What does the seminal fluid consist of?
secretions from:
- seminal vesicles,
- prostate,
- bulbo-urethral gland (Cowper’s gland)
- combined with epididymal fluid
What is the function of the seminal fluid?
- Transport of sperm through the male reproductive tract.
- Coagulation of the ejaculate and creating a sperm deposit in the vagina.
- Creation of a neutral to slightly alkaline buffered milieu in the vagina to protect spermatozoa from the acidic vaginal milieu.
- Activation and augmenting the motility of the sperm cells.
- Coating the sperm cells with capacitation inhibitors.
- Supplying nutrients for the sperm cells.
Describe the motility of sperm in the male reproductive tract
- non-motile
- seminal fluid aids in activation of motility
What is capacitation simply?
- Process that sperm cells undergo in order to fertilise
- capacitation before cervix = too early
- capacitation should ideally take place closer to site of fertilisation
What are the semen analysis limits set by WHO 2021?
What do the semen analysis limits by WHO 2021 measure?
- male fertility
What is a more expensive test for male fertility?
- Sperm DNA fragmentation
How long goes spermatogenesis last in ones lifetime?
- continuous from puberty, never stops.
Is spermatogenesis a short process and free of errors?
- NO
- Process is long and complex with many errors
=> high quantity, low quality
what is the objective of spermatogenesis?
- to produce high numbers.
What drives spermatogenesis?
- FSH
- Testosterone
Are sperm specialised for its function?
- Yes, highly specialised for function
What is the process of meiosis?