Folliculogenesis Flashcards
What is required to reproduce?
- Differentiation into male or female
- Sexual maturation
- Production, storage and release of sufficient supply of eggs and sperm
- Correct number of chromosomes in eggs + sperm
- Eggs and sperm have to meet ie. gamete transport
- Creation of new individual with genes from both parents
- To nurture individual until capable of “independent life”
What cells do oocytes or sperm differentiate from?
Primordial Germ Cells (PGCs)
When are PGCs first identified?
First identified in the yolk sac of the developing foetus three weeks after conception
Describe the cycle of primordial germ cells
- Undergo many cycles of mitosis to increase the number of PGCs
- They migrate to the genital ridge in the foetus
- The genital ridge becomes the gonad
- Further differentiation of the PGC into male/female gametes depends on the sexual differentiation/development of the gonads e.g into ovary or testes
What happens when PGCs enter the ovary?
Germ cells become oogonia when in the ovary
Describe what oogonia are?
Oogonia are egg-precursors that are diploid and multiply by mitosis
What is the process of oogonia to primary oocytes?
- Oogonia are diploid and multiply by mitosis
- Once mitosis stops they enter into meiosis and form primary oocytes
What is difference between male and female fertillity?
Women are born with an entire stock of eggs, when these are depleted we enter menopause
Men however do not have a defined fertillity
When are all the primary oocytes made?
Specify the particular stage.
- They are made when the oogonia enters the 1st stage of meiosis
- They remain in the first phase of meiosis until it is ovulated (or dies) - maybe up to 52 years
Explain the duplication of chromosomes
- Chromosomes replicate during S-phase
- Remain attached at the centromere
- Each copy is known as a chromatid, the 2 are identical ‘sister chromatids’
Give a brief description of mitosis
Prophase, Metaphase, Anaphase and Telophase
- DNA replication occurs in interphase and forms two sister chromatids which form a chromosome
- Sister chromatids seperate and move to opposite ends of the cell
- Spindle shorten pulling the sister chromatids apart to opposite poles
- Cytokinesis the parent cell divides, forming two daughter cells.
- Each daughter cell has two copies of each chromosome (46 chromosomes per cell)
Give an overview of meiosis
- Chromosomes line up adjacent to each other (paternal and maternal chromosome 1 line up)
- Homologous chromosomes pair and exchange genetic material = synapsis
- First division - chromosome number is reduced as the two homologous pairs are seperated into two cells
- Second division - the replicated chromatids of each chromosome are seperated
- Meiosis begins with one diploid cell and ends up with four haploid cells
- Both meiotic divisions has four stages similar to those in mitosis
What is the difference between oogenesis and folliculogenesis?
In oogenesis you will not get four mature eggs, but one mature egg with unequal division of cytoplasm during cytokinesis.
The rest is ejected as polar bodies
Describe the stages of oogenesis
- Oogonium
- Primary oocyte
- Secondary oocyte
- First polar body
- Mature ovum and polar bodies
Summary of folliculogenesis
- Primordial follicle forms around the primary oocyte - making one of the first granulosa cell layers
- Granulosa cells secrete an acellular layer called the basal lamina
- Primary follicle secretes another protective layer called the zona pellucida - stays attached after ovulation + plays a role in fertilisation
- Tertiary (Graafian) follicle - theca cell layers, follicle fluid filled antrum and granulosa cell layers
What is follicle growth driven by?
- Early stages of follicle growth are large unknown - granulosa cells multiply and oocyte enlarges (though remained in meiotic arrest)
- FSH will drive mose of folliculogenesis but early growth is independant of FSH + driven by local factors
What proof is there that follicle growth is driven by FSH and local factors?
Early growth is driven by local factors due to
Follicle growth being present in
- FSH-deficient patients or those with FSHr mutations
- When FSH is supressed e.g on COCP the follicles continue early growth and then die
What happens when there is a gonadotrophin surge at the middle of the menstrual cycle?
Stimulates re-entry of the oocyte into meiosis as far as metaphase II
Why does the oocyte need to be surrounded by layers of cells?
Surrounded by layers of protective cells as they are the most important cell in the body
What happens to the cells around the oocyte in the foetal ovary?
The surrounding cells condense around the oocyte and differentiate into granulosa cells
What do the granulosa cells secrete?
An acellular layer called the basal lamina
What is the structure of the primoridal follicle?
Granulosa cell and basal lamina
What is the ovarian reserve?
Build up of the primordial follicles at the beginning of birth
Folliculogenesis
The growth and development of follicles from the earliest ‘resting’ stages as laid down in the foetus, through to ovulation
What happens during follicle growth?
Granulosa cells multiply and the oocyte will secrete another protective acellular layer called the zona pellucida - stays attached after ovulation
Second layer of cells then differentiate around basal lamina - called the theca
- Theca has a blood supply allowing for influence of external hormonal influences
- As follicle starts to grow it increases in diameter and granulosa cell divisions increase, gaps form in granulosa cell layers
- Gaps consist of fluid flilled spaces forming an antrum and are filled with follicular fluid
What is an antrum?
Gaps in granulosa cell layers consisting of fluid filled spaces with follicular fluid
What divides the primary and secondary antral follicles?
Labelled by the presence or absence of an antrum
Describe the antral follicle
- Characterised by a cavity or ‘antrum’
- Contains fluid formed exudate of plasma containing secretory products of oocyte and granulosa cell
- Known as follicular fluid
- As the follicular fluid volume and antrum expands the oocyte is displaced to one side
Which follicles are not present on an ultrasound?
Follicle initiation - what is it?
A cohort of early follicles leave the resting pool and grow continuously
What is follicle recruitment?
The follicle will not continue to grow unless it reaches the sizr at which they respond to changes in FSH which occur in the menstrual cycle
Why is only one follicle recruited?
The human pelvis is only designed to carry a single foetus therefore only one will be selected for ovulation
How many cycles does it take for a follicle to go from resting stage to ovulation?
3 cycles
What parts of the cycle are gonadotrophin independant?
Primordial and pre antral
What parts of the cycle are gonadotrophin dependant?
Antral + Ovulatory
Describe the structure of the antral ovarian follicle
- Oocyte with cumulus cells surrounding it
- Follicular fluid
- Granulosa cell layer
- Basement membrane
- Theca layer
Why is the theca vasculature important?
Theca vasculature brings all the circulating influences particularly FSH and LH
What does the ovarian follicle produce?
Produces steroids
What is the 2-cell, 2-gonadotrophin theory?
- LH will bind to LH receptors on the theca cell = produces androgens and progesterone
- The granulosa cell layer will convert these to oestrogens which have FSH receptors and FSH will bind and stimulate aromatase
Describe how LH stimulates theca cells?
It binds to the LH receptor which stimulates the theca cell to turn cholesterol to androstenedione which is then released into the circulation
How does FSH stimulate granulosa cells?
- Androstenedione diffuses into the granulosa cell
- FSH binds to the FSH receptor
- Aromatase converts androstenedione into estradiol that is then released into the follicle
What receptors do theca cells have?
LH not FSH receptors
Which receptors do granulosa cells have?
Have FSH receptors and LH receptors
Why are LH receptors needed on granulosa cells?
- They are acquired from mid-follicular phase on
- The LH will drive progesterone and oestrogen production as well
How is folliculogenesis controlled?
- Hypothalamus releases GnRH into the anterior pituitary
- This then produces FSH/LH which stimulates the production of oestrogen and progesterone
- Then feedback influences the anterior pituitary and hypothalamus
What happens to a follicle if it doesnt make it to the menstrual cycle?
- Most will die through atresia, few make it into the menstrual cycle and even less ovulate
Describe the summary of folliculogenesis
- PGC differentiate into oogonia, proliferating by mitosis and enter into meiosis + meiotic arrest
- These then form primordial follicles
- There is basal growth of primordial follicles but these do not progress
- Once puberty commences, primordial follicles initiate growth as a continuum, until all follicles depleted and woman enters into menopause
- Eggs remain arrested in M1 until ovulation
- They then enter into M2 and arrest again
