Spermatogenesis and Male Tract II Flashcards
Is Testis development dependant on the pituitary?
What does this graph tell us?
- At any point, if you have a hypophysectomy (r\removal of the hypophysis (pituitary gland), and weighed the testis, the testis will regress, no matter what point of maturation/development!
- Therefore the pituitary is neccessary not only for testis growth, but for maintenance!
Is pituitary Function dependant on testis?
If you remove the testis (castration), and then measure its function (by measuring LH and FSH levels) you see a huge rise in these levels.
This is because there is no negative feedback of testosterone. (Like the male version of menopause).
What happens to anterior pituitary function if you add extra exogenous testosterone?
Exogenous or endogenous,it feeds back negatively, causing the hypothalamus/pituitary to release less LH and FSH for a few days.
This is why supplimentary steroids → reduced sperm count → infertility
Is there a direct relationship between LH and testosterone levels?
Yes.
LH and FSH are released in a pulsitile manner. As these (especially LH) are drivers of testosterone they stimulate following peaks of LH.
Learn and understant the
“Hormonal control of Spermatogenesis” chart on pg 33
- GnRH drives the system. Stimulates gonadotroph cells in the Anterior pituitary or ‘Pars distalis’ produces LH and FSH
- LH → stimulates Leydig Cells→ produce Testosterone
- FSH → stimulates Sertoli Cells → produces inhibin, ABP and other proteins
What’s the basic class of Gonadotroph cells?
Basophils (stain purple)
What is the role of Inhibin and how is it produced?
Negatively feedbacks on the gonadotroph hormone FSH.
GnRH → FSH → stimulates Sertoli Cells → inhibin
Testosterone can be transferred into _________.
How does this occur
Testosterone → eostrogen.
Occurs in fatty tissues, via the enzyme aromatase, the eostrogen can now also negatively feedback on the hypothalamus and the pituitary, the same as testosterone.
(the form of it doesn’t matter)
How is it that testosterone can also → eostrogen in Sertoli cells?
Because these cells also contain the aromatase enzyme!
Doesn’t tend to happen post-puberty, when now all the conversion occurs only in fatty tissues
What is ABP and how is it released?
Sertoli cells produce and release Antigen Binding Protein under the stimulus of FSH, which acts as a carrier molecule for circulating Testosterone!
As well as negative feedback on the HP-axis, where else does this testosterone go and what form is it in?
To target organs around the body,
In the male epididymus, prostate and seminiferous tubules.
BUT they prefer the stronger dihydrotestosterone (DHT), a more active form of testosterone.
How is DHT produced?
In both the Leydig and Sertoli cells.
Converted from T → DHT .
This gets feed into the circulation to target organs OR through secretions of the SN tubules/epididymus etc
Maintains function/secretions of continuous spermatogenesis
Why is the hypothalamus in the male system so important
Because unlike the female there is no positive feedback in the male HP axis! Only negative-feedback with a system driven by hypothalamus and its production of GnRH
What is the effect of T/DHT on spermatogenesis?
- Necessary for meiosis (esp. Prophase of 1st division, before the chromosomes line up)
- Necessary for spermatid maturation (all the phases): higher levels then (1)
- Stimulates ABP (so can stimulate it’s carrier, smart system!)
What would the FSH and LH levels of a hypogonadal man (non-function testis) look like and why?
In a normal man (T=5.8mg/ml) they are at a set, slightly pulsitile level.
In the lowering of T (T=3.8mg/ml) their LH and FSH are both elevated with lots of peaks, as there is less negative feedback on the H and P. Sperm count also lower.
Fix by intramuscular injections of Testosterone.
When you’re on Testosterone the peaks of LH _______
When you’re on Testosterone the peaks of LH get further apart. You get one single peak instead of mutliple .
If you give oestrogen the peaks of LH stay at a similar frequency, but they drop in amplitude
Whats the role of E2 in males
You need Oestrogen in males
- Part of the negative feedback control (via peripheral conversion of T to E2)
- Enhances the action of androgens
- Enduces fibromuscular growth in male accessory organs. E2 receptors in stromal tissues, A receptors in epithelial tissues
What was the conclusive finding of the ‘Aromatase knockout mice’?
Androgens couldn’t convert to estrogens
Female Mice: Follicles developed but couldn’t progress to ovulation. Some follicles didn’t develop at all. Replicated PCOS (where androgens overbalance estrogens).
Early follicles → SN tubules structure and developed Sertoli cells .
Therefore in the abcense of the enzyme you can begin to convert to a male.
Male Mice: spermatogenesis was interupted and stopped very early on
Easiest ways to distinguish testicular disorders?
Sperm count; if low, you can investigate further; measure FSH.
Obstructive Azoospermia: no sperm in semen, due to vasectomy. FSH levels normal.
Hypospermatogenesis (low sperm count): most have normal FSH, but if they start to rise this suggests not enough - feedback due to not enough testosterone
Geminal Cell Arrest: spermatagonia don’t develop properly
Sertoli-cell only syndrome: No germ cells, only abnormal sertoli cells! Have no inhibin → excessive FSH levels
Seminiferous tubule Hyalinization: v high FSH, everything glassy
Where does sperm maturation occur, how long does it take and what changes occur??
Occurs throughout epididymis, takes ~2weeks to pass through epididymis.
- Residudal cytoplasm absorbed → streamlined
- Increased formation of disulphide bonds in stuctural proteins (increases stiffness and changes swimming from thrashing →directed movement
- Increased surface charge
Concentration increases 100 fold, as fluid is reabsorbed (via vasa efferentia) sperm count goes from 50mill/ml to 5000mill/ml
Seminal Vesicles
Release up to 60% of the fluid found in semen. The other 40% is produced by the prostate and bulbourethral glands.
Contain (fructose, protein, prostaglandin and potassium)
Debris in lumen is old cells, ‘apocrine secretion’ where the tops of the cells break off and fluid is secreted.
**Prostate the same, but no apocrine secretion and the cells are very pale.
The ejaculatory ducts histology
Embedded in the prostate.
Folded surface, surrounded by smooth muscle which drives secretions from vas deferens → urethra
Physiology of Erection
- 1 corpra cavernosa (ventral, 2 corpus caverous make it up), 1 corpus spongiosum (dorsal)
- Relaxation of arterial and corpra smooth muscle leads to expansion of cavernosa → compressed venous outflow
- Relaxation is due to NO and its downstream messanger guanosine monophosphate
- Guanosine monophosphate is broken down by phosphodiesterase-5
- Inhibitors of PD-5 promote relaxation/erection; viagra, cialis, levitra
What Features should you look at in an Assessment of Male Infertility
- Liquification: should occur <15 mins
- Volume <1ml a problem
- Sperm Concentration <15x106 a problem
- Motility <40% active sperm a problem
-
Grade of motility
- 3 Good forward progress
- 2 Moderate forward progress
- 1 Poor
- 0 Twitching
- Morphology >70% abnormal usually infertile
- Debris inc WBC; sign of infection; BAD SIGN
If >3 of these are below optimum, then it’s likely fertilisation won’t occur
