The Male Tract: Testis and Spermatogenesis Flashcards
What are the 3 functions of the male reproductive system?
- Production of androgens
- Production, storage and nourishment of male gametes
- Introduction of male gametes into the female reproductive tract
Histology of the testis
- Tunica albuginea divides the testis into approx. 300 lobules
- Each lobule contains 1-4 seminiferous tubules
- The seminiferious epithelium is formed by two cell populations – the cells of spermatogenic lineage, and the resident sertoli (sustentacular/nurse) cells.
- Leydig cells are interstitial cells between the seminiferious tubules. They are involved in the endocrine function of the testis.
What are the 6 functions of the Sertoli/Nurse/Sustentacular cells?
- Maintenance of tbe blood-testis barrier → sertoli cells are joined by tight occluding junctions. Transport across the cells is tightly regulated. The barrier prevents the immune system from attacking sperm.
- Support of mitosis and meiosis → FSH and testosterone stimulate the sertoli cells, and these cells then promote the division of spermatogonia and spermatocytes
- Support of spermiogenesis → The sertoli cells surround and enfold the spermatids, providing nutrients and chemical stimuli that promote their development. They also phagocytose the cytoplasm shed by spermatids
- Secretion of inhibin → This depresses pituitary production of FSH, and GnRH. The faster the rate of sperm production, the more inhibin produced – this provides feedback control.
- Secretion of Androgen Binding Protein → this binds androgens in the seminal fluid. Thought to stimulate spermiogenesis
- Secretion of Mullerian Inhibiting Factor → Causes regression of the mullerian ducts in the developing testis.
Describe spermatogensis
. Mitosis (spermatocytogenesis)
• Spermatogonia (stem cells) divide by mitosis to produce two daughter cells, one of which remains at the location as spermatogonium, the other differentiates into a primary spermatocyte.
• There are several rounds of this mitosis – this is the proliferative phase
• Glial cell-line derived neurotrophic factor (GDNF) was identified as a critical factor for the replication of spermatogonia
• These cells look like conventional cells in the body, don’t have any features of sperm yet
- Meiosis I
• Primary spermatocytes divide, giving two diploid daughter cells
• These are known as secondary spermatocytes - Meiosis II
• Secondary spermatids divide to produce four haploid spermatids – immature gametes - Spermiogenesis
• The spermatids develop into mature spermatozoa
• These lose contact with the wall of the tubule, and enter the fluid in the lumen
What gene encodes a protein that anchors the sperm nuclear membrane to the acrosome cap?
DPY9L2
Describe the structure of sperm
Head
• Flattened ellipse containing a nucleus with densely packed chromosomes
• At the tip of the head is the acrosome
• DPY9L2 gene encodes a protein that anchors the nuclear membrane to the acrosome cap
Mid Piece:
• Neck attaches the head to the mid pieces – contains both centrioles of the original spermatid, forming an axoneme
• Mitochondria are helically arranged, providing ATP for moving the tail
Tail:
• The only flagellum in the body
How does sperm have motility?
- Tail contains microtubules and dynein (an ATPase)
- Hydrolysis of the ATP generated in the adjacent mitochondria provides energy for motility
- However, sperm are not motile in the seminiferous tubules, they mature and become motile in the epididymis as a result of DHT
- Further maturation occurs in the female tract (capacitation)
Describe spermiogenesis.
- Reduction in the size of the nucleus and condensation of the chromosome material → DNA isn’t very active in sperm, so it condenses to become compact for fertilization
- Reorganisation of the cytoplasm. Condensation of the golgi at the apical end gives rise to the acrosome. The acrosome is essential for fertilization – it contains hyaluronidase, which is released as sperm reach the oocyte to digest the zona pellucida.
- The flagellum grows out of the centriole region. Mitochondria arrange in a spiral around the proximal flagellum.
- The remainder of the cytoplasm (residual body) is shed along the tail, and phagocytosed by sertoli cells.
- The sperm is then released into the lumen.
What is globozoospermia?
- The production of round headed sperm.
- Cannot fertilise, because they have nor developed an acrosome cap
- The defect is often genetic → the DPY9L2 gene is mutated in many cases. Inheritance is autosomal recessive.
Pierre et al, 2012
− Used DPY9L2 knockout mice to describe the function of the gene
− Show that the protein is expressed predominantly in spermatids with a very specific localization restricted to the inner nuclear membrane, facing the acrosomal vesicle.
− The absence of DPY9L2 leads to the destabilization of both the nuclear dense lamina and the junction between the acroplaxome and the nuclear envelope
− Consequently, the acrosome and the manchette fail to be linked to the nucleus, leading to a disruption of vesicular trafficking, failure of sperm nuclear shaping and eventually to the elimination of an unbound acrosome vesicle.
Brinster, 2007
Expert in male germline stem cells.
- Spermatogonial cells are the only germline stem cells in adults – female germline stem cells cease proliferation before birth.
- There are no known unique phenotypic markers for distinguishing SSCs from their initial daughters (spermatogonia)
- Similar to embryonic stem cells, SSCs stain positive for the Pou domain class 5 transcription factor 1, Sox2, Oct-4 and alkaline phosphatase, but Nanog – a key determinate of ESC pluripotency is not expressed. So doesn’t seem they are pluripotent - now commonly acceptaed that SSCs are unipotent.
Recent advances suggest they have applications in infertility treatment.
• SSCs can be isolated from testis tissue
• They can be transplanted into a recipient teste, into the seminiferous tubule
• The transplanted cells can develop into competent spem.
Who is Nathan Crawford?
A nine-year-old boy with a brain tumour has become the first person in the UK to have his testicular tissue frozen so that he will be able to father children in later life.
Nathan Crawford, of Bude, Cornwall, has undergone radiotherapy and chemotherapy to shrink his inoperable tumour but it is possible the treatment has left him infertile.
Currently, it is not possible to preserve the fertility of pre-pubescent boys undergoing some cancer treatments, because they do not produce sperm.
However in a ground-breaking procedure, surgeons at the John Radcliffe Hospital in Oxford removed a wedge of testicular tissue and froze it before his treatment.
It means that if Nathan does suffer infertility in later life, and wants to become a father, he will be able to have the tissue transplanted. No child has yet been born from transplanted testicular tissue
Sperm production: the figures
- Each spermatogonium → 16 primary spermatocytes
- Each primary spermatocyte → 4 spermatozoa
- So each of the 3 million spermatogonia that begin the process EACH DAY give rise to 64 spermatozoa
- About half die
- Leaves ~108 per day
- Sperm formation takes 70 days, followed by 14 days to reach the ejaculatory ducts
Sperm production and fertility
- Fertility clinic threshold – approx. 20 million per ml
- As sperm numbers increase, you don’t really see a difference in the number of pregancies
- However, levels of semen production can fluctuate naturally → so if you are going to evaluate fertility, you shouldn’t do a one off measurement.
‘Normozoospermia’ Values
- Volune > 2ml
- Sperm > 20million per ml
- Output > 40million per ejaculate
- Motility > 50% of the total
- Normal morphology > 30%
- White blood cells
