Folliculogenesis Flashcards
What are the main stages required for human reproduction to occur?
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”
How do germ cells enter the gonad?
PRIMORDIAL GERM CELLS
= precursors for eggs/sperm
- PGCs found in yolk sac at 3 weeks gestation
- PGCs undergo mitosis cycle
- migrate to genital ridge in foetus
- genital ridge then becomes the gonad
- Differentiation of the PGC into gametes (M/F) depends on sexual differentiation of the gonads
What happens when PGCs enter the ovary?
PGCs = primordial germ cells
They become OOCYTE IN THE OVARY
- become oogonia in the ovary
- oogonia are precursors to the egg, are diploid and therefore multiple my mitosis
- when mitosis stops, they enter meiosis (PRIMARY OOCYTES)
- once they enter meiosis, cells become quiescent (arrest in G0)
What is the ‘Ovarian reserve’?
idea that all the eggs a woman will ever have are made within gestation of that foetus
What happens when oogonia enter meiosis I?
no more division occurs
become primary oocytes
these remain arrested in G0 until ovulated (and then fertilised)
What are the 4 main stages of mitosis?
prophase
metaphase
anaphase
telophase
What is meiosis?
2 divisions
meiosis I: similar to mitosis, duplication and separation of chromosomes (4n -> 2x 2n)
meiosis II: further division of 2n cells -> 2x n (haploid gametes are result)
What is the structural difference between mitosis vs meiosis and meiosis I vs meiosis II?
chromosomal alignment
meiosis I: sister chromatic pairs line up at equator
meiosis II: individual chromatids line up at the equator
What is the follicle?
egg surrounded by a single layer of granuloma cells
What is distinct about the divisions in oogenesis?
unequal division of cytoplasm during cytokinesis
produces daughter cell and polar body
What is the function of the retained cytoplasm in the main egg (in oogenesis)?
used for nutrition
helps development of egg/embryo
Where are primary oocytes stored? How is the structure adapted to this?
packed into the outer layer of the ovary = CORTEX
Cortex is AVASCULAR - allows greater packing of primary oocytes here
What are the protective layers surrounding an oocyte in the ovary?
- [in foetal ovary] surrounding cells condense and form GRANULOSA CELLS
- granulosa cells secrete the BASAL LAMINA (acellular layer)
Together this is the PRIMORDIAL FOLLICLE
What is comprised in the primordial follicle?
oocyte + granuloma cells + basal lamina
[develops in foetal ovary]
How are the primordial follicles affected perinatally?
The number of primordial follicles postnatally determines the ovarian reserve and reproductive lifespan
What happens when the ovarian reserve of primordial follicles is depleted?
menopause
What is folliculogenesis?
growth and development of follicles
from the earliest stages in foetus to ovulation
What is the nature of follicular growth in ovaries?
most are NOT growing.
After puberty, a subset of follicles will start growing but v. slowly and tightly regulated
What happens when folliculogenesis begins after puberty?
granuloma cells multiply
oocytes secrete the ZONA PELLUCIDA (protein-rich acellular layer)
ZP remains attached after ovulation
After initiation of follicular growth, a second layer of cells differentiate around the basal lamina: the THECA
How is the THECAL layer formed?
condensation of stromal cells surrounding oocyte
occurs at same time as formation of zona pellucida
What is the regulation of follicle growth?
initiation of process and early stages are largely unknown
granuloma cells multiply oocyte enlarges (though still in meiotic arrest)
What factors drive folliculogenesis?
GENERAL: FSH main regulator for folliculogenesis
early growth: FSH-independent, driven by local factors as cortex is avascular so no systemic hormone entry
late growth: FSH-dependent (astral follicles)
What are the main stages occurring in follicular growth?
follicle rapidly increases in diameter + granulosa cells divide more
gaps form between granulosa cell layers
gaps = follicular fluid filled spaces, form an antrum
= antral follicles
What are the 2 main types of follicles?
Pre-antral follicles (FSH-independent)
Antral follicles (FSH-dependent). Theca, which is vascularised, has formed by this stage, so hormones from systemic circulation can enter
What are the (alternative) names for the different types of follicles?
Primary (Pre-antral)
Secondary (Antral)
Pre-ovulatory (Graafian)
What stages produce an antral follicle?
migration of granulosa cells towards edge
formation of cumulus cells (surrounded by fluid filled antrum)
fluid is formed by transudate of the plasma (neoangiogenic capillaries) surrounding follicle
What is an antral follicle?
contains cavity = antrum
antrum contains fluid formed as plasma exudate
FOLLICULAR FLUID = contains secretory products from oocyte and granulosa cells
asymmetric displacement of oocyte as antrum fills
Which types of follicles are not visible by USS?
pre-antral follicles
but are present all the time until menopause
What is follicular atresia?
death by apoptosis
regression following thinning of membrane and eventual death
Which follicles undergo folliculogenesis?
- cohort of early follicles, which leave the resting pool to grow (FOLLICLE INITIATION)
- will not continue to grow unless they reach size at which they are FSH-sensitive (to changes in menstrual cycle) FOLLICLE RECRUITMENT
- however only one follicle (DOMINANT FOLLICLE) will be selected for ovulation in one cycle
- remaining follicles will die off by atresia
How does the COCP affect folliculogenesis?
will have small follicles and will still grow
however lack of FSH mean that antral follicles are not ovulated and just die instead
What is the function of the zona pellucida in fertilisation?
prevents further sperm entering (after one has got in)
therefore prevents POLYSPERMY and ANEUPLOIDY
What hormone is produced by granulosa cells?
oestrogen
What hormone is produced by theca cells?
androgens
What is the importance of the vasculature in theca cells?
follicle can now be exposed to hormones that travel in the systemic circulation
e.g. FSH
What is the 2-cell-2-gonadotrophin theory in folliculogenesis?
LH stimulates thecal cells to produce androgens
FSH stimulates granulosa cells to produce oestrogen from androgens (via aromatase)
only granulosa cells have aromatase - this is FSH-dependent
theca cells have only LH receptor
granulosa cells have both LH and FSH receptors
What happens to androgens produced by theca cells?
may enter systemic circulation
or have autocrine effects on follicle
When is the theca formed in folliculogenesis?
during the pre-antral stage
What is the role of theca cells in steroidogenesis?
contains LH-R only
LH drives androgen and progesterone synthesis from theca
What is the role of granulosa cells in steroidogenesis?
contain FSH-R: FSH drives oestrogen production in follicular phase of menstrual cycle
LH-R are acquired from the mid-follicular phase onwards (in dominant follicle)
LH then drives progesterone and oestrogen production too
What is the HPG axis control of folliculogenesis?
hypothalamus: GnRH
pituitary: LH/FSH
ovary: oestrogen and progesterone
=> negative feedback on hypothalamus and anterior pituitary
What occurs during ‘foetal development’ stage of folliculogenesis?
PGCs differentiate into oogonia
Proliferation by mitosis
Enter meiosis and arrest in G0
Form primordial follicles
What occurs in the ‘postnatal stage’ of folliculogenesis?
Some basal growth of primordial follicles
But no further progression
What occurs in the ‘post-pubescent stages’ of folliculogenesis?
[Once puberty commences]
Primordial follicles grow continuously until menopause
eggs remain arrested in meiosis I until ovulation
The egg then completes meiosis I, enters meiosis II and then arrests again (until fertilisation)
What is aneuploidy?
high risk in older eggs (>35yo), presence of abnormalities in egg
e.g. defects in spindle proteins or abnormal chromosomal number
increased risk of complicated pregnancy or congenital issues
