Spermatogenesis Flashcards
Major functional components of the testes?
- Seminiferous Tubules - ~250m total length, has developing germ cells and sertoli cells.
- Interstitial Spaces - have leydig cells (synthesise androgens) and blood & lymph vessels.
- Compartments held by separate by blood-testis barrier which prevents immune response to spermatozoa and separates fluid of different composition.
3 stages of spermatogenesis
- Mitotic proliferation
- Meiotic divisions
- Cell modelling (spermiogenesis)
Spermiation
At the end of differentiation; cytoplasmic links are broken, spermatozoa released into tubule lumen, and sperm are virtually immobile.
Fluid secreted by Sertoli cells flushes spermatozoa from seminiferous tubules, through the Rete Testis into the Epididymis: Capacity for motility by the time they reach the tail of the epididymis, motility is suppressed by epididymal fluid and instead movement through reproductive tract is aided by peristaltic muscle contractions.
Spermiogenesis
Spermatocyte > Spermatid > Spermatozoon
About 200million/day (approx. 2300/second)
Spermatogenic Cycle
Stem Cell > Type A Spermatogonia > Intermediate Spermatogonia > Type B Spermatogonia > Resting Primary Spermatocyte > Stages of meiosis (leptotene, zygotone, pachytene, diplotene) > secondary spermatocyte (formed by first meiotic division) > spermatid (formed by second meiotic division) > Spermatozoon.
Average length of Spermatogenic Cycle?
~74 days from 1st mitotic division to release of spermatozoa.
Spermatogenesis - Rate of each developmental stage?
- Spermatogonium - Primary Spermatocyte - 25 days
- Meiotic Division 1 - Secondary Spermatocyte - 9 days
- Development - Spermatids - 19 days
- Differentiation - Spermatozoa - 21 days
Processes of Sperm Maturation
- Development of motility
- Nuclear maturation
- Water loss
- Acrosome changes shape
- Surface charge changes
- Permeability of membrane changes
- Cytoplasmic droplet is shed
- Cellular lipid reserves are depleted
- Sialic acid glycoprotein coat is gained
Changes made to the Spermatozoa in the Epididymis
- Concentration - 10-fold (10^8/ml entering > 10^9/ml leaving)
- Sperm modelling - nuclear condensation and acrosome shaping completed. Cytoplasmic droplet is shed.
- Metabolism - increased dependent on extracellular fructose for glycolytic energy, little oxidative metabolism, increase intracellular pH (due to Na+/H+ exchange).
- Motility - increased disulphide bridges between proteins in outer dense fibres of tail. increased concentration of cAMP in the tail. Acquires the capacity for forward movement.
- Membrane - composition changes.
Sub-fertility
- Human sperm quality is poor - only 4-14% show normal morphology under the microscope.
- If normal morphology drops below 4% fertilisation rates obtained with IVF are reduced.
- Infertility in men is primarily diagnosed by semen analysis comprising of: determination of sperm concentration/total count, motility, morphology.
Oligozoospermia
Reduced sperm count (<15million/ml)
Azoospermia
Absence of sperm in the ejaculate
Asthenozoospermia
Reduced sperm motility (<40% moving)
Teratozoospermia
Reduced percentage of sperm with normal morphology
Anti-sperm Antibodies
Abnormal immune response to sperm
Roles of Hypothalamus and Pituitary in Spermatogenesis
Hormones released by the hypothalamus, pituitary and testes sre regulated by feedforward and feedback loops. Hypothalamic secretion of Gonadotrophin-releasing hormone (GnRH) stimulates the release of gonadotrophins from the anterior pituitary. Pituitary gonadotrophins, luteinising hormone and follicle-stimulating hormone control testicular functions.
Control of Gonadotrophin Secretion
- LH and FSH secretion is controlled by GnRH secreted by the hypothalamus.
- GnRH is released into the portal blood in pulses every hour.
- GnRH must be pulsatile or it is ineffective.
- High GnRH pulse amplitude and frequency preferentially stimulates LH synthesis and secretion whereas low GnRH pulse frequency stimulates FSH synthesis and secretion.
Anterior Pituitary Hormones
- Gonadotrophs - secrete LH and FSH (glycoproteins), most cells secrete one or other, but some secrete both.
- Lactotrophs - secrete prolactin (protein)
Posterior Pituitary Hormones
- Neurosecretory neurones - secrete arginine vasopressin (AVP) and oxytocin (peptides).
Functions of Luteinising Hormone and Follicle Stimulating Hormone in Spermatogenesis
- Luteinising Hormone - stimulates synthesis and secretion of testosterone in Leydig cells. If LH is too low, testosterone is low and spermatogenesis halts.
- Follicle Stimulating Hormone - required for maximum sperm production and acts on Sertoli cells. Increased androgen receptors, increased FSH receptors. FSH increased RNA and protein synthesis, increased fluid secretion, increased inhibin synthesis and secretion, increased ABP secretion, increased cAMP and cell metabolism.
Testicular Hormones
- Testosterone - steroid hormone made by the Leydig cells. In some tissues it does not exert direct effects but are converted to dihydrotestosterone or oestrogens
- Oestrogens - steroid hormone made by the aromatisation of Testosterone in Sertoli Cells
- Inhibins - peptide hormone made in Sertoli cells, helps with the feedback loop to control hormone levels
- Oxytocin - peptide hormone made by Leydig cells. Causes contraction of smooth muscle of the genital tract.
Role of Testosterone in Spermatogenesis
Essential for spermatogenesis, if not produced spermatogenesis ceases. It is blocked when primary spermatocytes enter the meiotic prophase.
If blood testosterone concentration is low then fewer stem cells will begin to divide but the whole process of spermatogenesis will still take 74 days.
Causal Diagnosis of Male Infertility
- It is not very common for men to receive a causal diagnosis of why they are infertile (~28%); most consist of previous gonadotoxic chemo- or radio-therapy for the treatment of malignant disease (~10%), testosterone abuse or other chronic diseases (e.g. diabetes; ~14%), or genetic disorders (e.g. Klinefelter’s syndrome, Karyotype 47, XXY or microdeletions on the Y-Chromosome; 4%).
- In addition, genes involved in the migration of GnRH neurons or upstream regulators have been discovered that may be mutated in patients with congenital hypogonadotropic hypogonadism with or without anosmia.
- Thus ~72% of men in infertile couples, no causal diagnoses can be established and the aetiology of distubed spermatogenesis remains unclear.
