gametogenesis Flashcards
(40 cards)
the hypothalamus is where? has roles in what? is connected to? role in HPG axis?
so its part of the diencephalon.
roles = homeostasis e.g. metabolism, Growth, reproduction + stress
connected to anterior pituitary through neural and vascular connections (hypophyseal portal system)
role in HPG axis = produces and secretes the neuropeptide GnRH
the pituitary gland is made up of multiple cell types responsible for secreting different hormones. Which cells produce which hormones relevant to HPG axis?
In the HPG axis - Gonadotrophs (Follicle-stimulating hormone; FSH and Luteinising hormone; LH)
what cells in the ovaries and testes respond to FSH and what do they produce as a result?
What cells in the ovaries and testes respond to LH and what do they produce as a result?
Sertoli cells responding to FSH - oestrogen (fluid absorption) ; inhibins and activins, ABPs (maybe androgens from leydig precursors?)
(female) Granulosa cells responding to FSH - oestrogen and progestogens (luteal phase); inhibins and activins
Leydig cells responding to LH - androgens (testoserone), bit of progesterone (spermiogenesis + capacitation)
(female) Thecal cells responding to LH - androgens (and progestogens?)
all the sex steroids -progestogens, androgens (testosterone, dihydrotestosterone, androstenedione) and oestrogens - are made from cholesterol precursor. there action is dictated by…?
their main function is…?
Action of these steroids is dictated by tissue-specific receptors.
Main function: normal reproductive development, gametogenesis and the maintenance of secondary-sex characteristics. They are involved in feedback systems too, but this is secondary
what positively regulates/encourages GnRH release?
KiSS1 neurons produce the 54 Aa neuropeptide kisspeptin, which binds to KiSSR in GnRH neurons and stimulates GnRH production
whats (at least in my head) the counterpart of kisspeptin, i.e. something that inhibits GnRH release (and how does it do so?)
RFRP-3. Or RFamide-related peptide 3 acts on KiSS-1 neurons and GnRH neurons in hypothalamus to reduce GnRH output. (also acts on gonadotrophs - pituitary - by suppressing the signalling cascade responsible for LH and FSH expression)
what else exhibits negative feedback on GnRH production?
- steroid hormones - produced by gonads, bind to KiSS-1 +ve neurons, providing negative feedback, less kisspeptin less GnRH
- the kisspeptin-GnRH axis, and therefore the HPG axis, is metabolically gated.
Factors related to metabolism and proper energy balance - insulin, ghrelin and leptin - act on the Kisspeptin-neurons, regulating Kisspeptin production and release.
Leptin key, a necessary factor for puberty to proceed. more body fat = more leptin, it acts directly on Kiss-1 neurons and others, to indirectly increase GnRH. So infertility issues can be seen in those with very little fat (or too much)
what does GnRH do in the pituitary?
binds to GnRHR on gonadotrophs, stimulating proliferation and causing a signalling cascade to upregulate expression of FSH, LH and the GnRHR
does anything cause positive feedback at pituitary (gonadotrophs)?
yes - activins (TGF-B family) increase FSH expression
negative feedback at the pituitary - what exhibits it and how?
Progesterone, testosterone and oestrogen. Enter the cell (gonadotrophs) and bind with their internal receptors (e.g. ER for oestrogen) and the hormone-receptor complex translocated to the nucleus to negatively control transcription of the target genes, reducing FSH, LH and GnRH-R production
Inhibin
decreases FSH expression AND dampens the response to activin by interfering with it’s receptor.
and as said already RFRP-3 supresses FSH and LH signalling cascade
describe the manner in which GnRH is released.
bonus - is it essential to gonads?
It is released in a PULSATILE nature, roughly every hour. These ‘pulses’ begin at puberty and the ‘pulse generator’ resides in the hypothalamus
It is therefore obvious that Anterior pituitary hormones are also released in a pulsatile manner in post-pubertal humans
bonus - Its been demonstrated that GnRH is essential for gonadal function as gonadal atrophy has been observed after destroying GnRH neurons, in genetically null GnRH mice, and in mice immunised against the GnRH peptide
give an overview of the anatomy of the testes relevant to spermatogenesis
spermatogenesis occurs in semin. tubules lined with semin. epithelium where sertoli cells are also
tubules organised into lobes separated by stroma. stroma = blood + lymph vessels + leydig cells
as sperm develop, move from outside @ basement membrane to central lumen (centripetal direction)
rete testes - vas efferentia - epididymis, stored here. ejaculation occurs - sperm goes to urethra via vas deferens.
its the seminal vesicle that + prostate gland that produce fluid for movement + alkaline secretion to neutralise acidity of urine in urethra respectively
outline the very early starting point for spermatogenesis - PGCs
First identifiable at 3 weeks gestation, the PGCs divide by mitosis and migrate to the genital ridge primordium, and so do the ‘germinal epithelium which become sertoli cells (male) and granulosa (female)
what is spermatogenesis/overview?
explain what happens to spermatogonial stem cells for them to become primary spermatocytes.
Spermatogenesis -
Starts at puberty, a SSC ends up producing four mature spermatozoa. Involves mitosis and meiosis, produces 100 million sperm a day.
Spermatogonial stem cells are what the PGCs develop into in males. They are adult stem cells that self renew (first part of diagram) as in when they divide by mitosis, the division is asymmetric, regenerating SSCs, but also if signalled by the microenvironment, one daughter cell may commit to spermatogenesis…
These are (1a) type A spermatogonia, and are morphologically distinct, emerging at intervals (around 16 days?) these undergo rounds of mitosis to produce 16-cell clone, which are a syncytium connected by cytoplasmic bridges.
Further rounds of mitosis + differentiation result in (1b) type B spermatogonia
More mitosis results in production of primary spermatocytes (still 2n)…
so PGCs = SSCs –> primary spermatocytes…
What are the next three stages? (
hint - meiosis, spermiogenesis - spermiation)
Primary spermatocytes
Undergo MI to produce haploid secondary spermatocytes
Secondary spermatocytes
Undergo MII to produce four round cell spermatids
Spermatids
Undergo spermiogenesis to produce four equally sized, genetically unique spermatozoa with the typical shape
Spermatozoa
Not yet fully mature - but they are fully differentiated and get released into the tubule lumen (this is spermiation). Some maturation still to be done in epididymis and female tract
what changes occur in spermiogenesis?
okay so this is when the round spermatid cells get the shape of a sperm cell - a spermatozoa…
Golgi apparatus forms acrosome cap
Nucleus changes shape to fit into the sperm head
KEY Massive repackaging of the DNA: histones are replaced by protamines to allow for greater compression of chromatin, no gene expression
One of the centrioles of the spermatid elongates to become the tail
The remaining cytoplasm and organelles = the residual body. This is removed by the sertoli cells by phagocytosis
sertoli cells - where are they and what is there structure like?
Where - span across the whole length of the seminiferous tubules, from basement to lumen
Structure - maintain close contact with eachother via tight junctions, forming a barrier to macromolecules called the blood-testis-barrier. This separates testes into basal and adluminal compartments.
They are also in contact with developing germ cells across all stages of development
Spermatocytes cross into the adluminal compartment once they have initiated MI
what is the need for the blood-testes-barrier?
Adluminal compartment is an ‘immune-privileged site’ protecting the haploid cells from potential immune rejection
explain the regulation (in terms of timing) of spermatogenesis.
How do sertoli cells regulate spermatogenesis?
The whole process of spermatogenesis in humans takes 64 days. The lag time between development of clones - that is a new group of spermatocytes entering spermatogenesis is 16 days. This means that a transverse section through tubule will reveal populations at four distinct stages
For this constant production 100 million mature sperm a day,, different sections of tubule must be at different stages
To achieve this the sertoli cells use their gap junctions to communicate from the basement to the lumen (and vice versa) in order to exert this spatial and temporal control
do the germ cells contribute to the regulation of spermatogenesis or is it just sertoli cells?
germ cells DO as well as sertoli, study that transplanted rat SSCs into mouse seminiferous tubules showed the sperm developed as normal but imposed rat timing on spermatogenesis
what do the Leydig cells produce, and what do these things do?
Androgens (Testosterone) covered in a sec, but sperm maturation…
Oestrogen - required for fluid absorption in the vas efferentia of the testes
Progesterone - supports spermiogenesis, capacitation and testosterone synthesis
Oxytocin - stimulates seminiferous tubule motility
Prolactin - enhances LH stimulation of Leydig cells
what do the sertoli cells produce?
Produce inhibin and activin (opposite feedback on gonadotrophs producing FSH at pituitary, also inhibin reduces activin impact, AND inhibin B has a stimulatory effect on leydig cells)
Also produce oestrogens → this is them converting testosterone and androstenedione produced by the leydig cells
Can’t forget androgen binding proteins, important in transporting sex steroid hormones to place of action
what are 5 roles of testosterone produced by the Leydig cells?
Acts on sertoli cells, contributing to maintenance of the blood-testis barrier; sertoli-spermatid adhesion; spermatid elongation; spermiation; production of testicular fluid
Within the sertoli cells, testosterone is converted to dihydrotestosterone and oestrogen which further stimulate Sertoli cells and support spermatogenesis
Testosterone travels to the tubule lumen, binds to androgen binding proteins (ABP) secreted by the Sertoli cells. Testosterone-ABP travels to and stimulates the ducts of testes
Feedback - autocrinologically on Leydig cells in negative feedback loop, and on gonadotrophs and KISS1 neurons (negative also)
Testosterone is also essential for the development of male secondary sex characteristics
two main functions of the female reproductive system?
this explains why the menstrual cycle is episodic in nature…
Function 1 - Gamete production and transportation
Function 2 - Site of implantation; support foetal development
This is a lot more to handle than the male reproductive system, which is why the menstrual cycle is episodic in nature, to facilitate these two different functions -
During the first (oestrogenic) half, a mature oocyte is produced and made ready for fertilisation;
In the second (progestagenic) half the uterus is made ready to allow implantation and to support pregnancy