are going to be primordial follicles and very
small primary follicles. Well, here’s a
histological section of a primordial follicle.
It’s an oocyte, and the oocyte is surrounded
by follicular cells. These cells were originally
stromal cells recruited from the stroma in
the cortex, and they wrap around the oocyte
and they protect it. They are supporting cells.
And then those stromal cells, when the oocyte
starts development, develop into what we call
follicle cells. Well, these oocytes, these
primordial follicles, as I mentioned earlier,
are present at birth. In fact, about the third
month of fetal life in the ovary, cells develop
into oogonia, the germ cell. And these undergo
massive mitotic activity. Until about the
fifth month of fetal life, you could have
five to seven million of these oogonia in
the fetal ovary. They’re actually in the
first meiotic division on their way to becoming
haploid cells containing half the number of
chromosomes and half the amount of DNA through
the process of meiosis. But meiosis is not
completed in these oogonia until adult life.
In fact, the final stage of meiosis is never
completed unless the oocyte undergoes fertilization,
which is very very rare. Now, of the five to
seven million of these oogonia that develop,
by the time the child is born, the female
child, there are about 400 to 500 of these
remaining. In other words, there’s a loss, an
enormous loss of this during fetal development,
until the only left at birth were 20% of these
oogonia and oocytes. And that’s because
those supporting cells I mentioned earlier
around them in the fetal ovary die off.
They withdraw their support so the oogonia die.
Now, of the 400,000 to 500,000 oocytes that
are there at birth, you’re only going to
have, in a normal reproductive lifespan of
the female, about 400 eventually ovulating.
The reproductive life of the female begins
at about at an average age of 12.7 years.
It’s called the menarche, and then menopause
or the cessation of the reproductive life
in the female is around the age of between
47 and perhaps 55 quite variable. But during
that reproductive life, ovulation occurs once
every 28 to 30 days as part of the ovarian
cycle, part of the menstrual cycle that lasts,
as I said, about 28 to 30 days. So there is
this enormous attrition of these follicles,
these oogonia, these oocytes. If we now look
at primary growth of the follicle, it’s
illustrated on this slide here, showing you
two sections through the ovary, two sections
showing you a primary follicle at various
stages of its development. First of all, when
a follicle changes from being a primordial
follicle to a growing primary follicle, the
stromal cells adapt a cuboidal type epithelium
that you see on the left-hand image and labelled.
This is the time at which you now define that
growing follicle as being a primary follicle.
If it has only got one layer, sometime it’s
referred to as being a unilaminar primary
follicle. If it has got many layers, such as
the one on the right-hand side, many layers
are often termed the membrane granulosa, then
we often call them multilaminar primary follicle.
Notice the size of the oocyte. Even though
these are taken at different magnifications,
during this phase of development, the oocyte
can change from being about 30 microns in
diameter up to about 50 to then 80 microns
in diameter. So there is enormous growth also
of the oocyte. We often term the oocyte as
being a primary oocyte. Not because it’s
part of a primary follicle, but because it’s
only in its first meiotic division stage.
It has not yet even completed its first meiotic
division. And it won’t do so until ovulation
if the follicle ever gets to the stage of
ovulation. Now, what happens during this stage
is that when these primary follicles develop,
they have this single layer, then they do
that independent of the gonadotropins from
the pituitary. But then when they get to a
certain stage, they’re dependent on follicle
stimulating hormone coming out from the anterior
pituitary gland. And that follicle stimulating
hormone causes these granulosa cells, that
they are now called, to multiply, to massively
divide. And as they divide, they give rise
to the membranic granulosa you see there,
multi-layers of these granulosa cells.
And those cells also, under the influence of FSH, produce
estrogens. Now, if you look very carefully
at the capsule around the multilaminar follicle
shown in this slide, you can just make out
sort of a capsule, a bit of tissue wrapping
around the cell, the follicle. That’s called
the theca interna and the theca externa layers.
Unfortunately, in a lot of histological sections,
you don’t see details of these separate layers.
But as I mentioned at the very start,
the theca externa is a connective tissue capsule.
The theca interna is a capsule that is very vascular.
And as development starts, as these follicles
begin to secrete estrogens in response
to FSH, they only do so because the theca
interna cells, the internal ones that are
around the follicle, they become steroidogenic
as well. They develop little lipid droplets
inside them, cholesterol droplets that are
the precursor for making steroid hormones.
And this theca interna layer, under the influence
of luteinizing hormone, or LH, synthesize
androgens. And those androgens pass across
the basal lamina separating the membrana granulosa
from the theca layers. And those androgens
are then used by the granulosa cells to make
estrogens because they don’t have the enzymes
to produce estrogens from the very precursor
products. So there is this combination between
the theca interna and the granulosa layers.
One provides the androgens, and the other
then using those to convert those androgens
to estrogens. And as the follicle grows, then
more estrogens produced. And therefore, during
the follicular phase of the ovary cycle, estrogens
will increase their levels in the blood.
Also, you can see in the image, in the picture on
the right-hand side, a shell around the oocyte.
It’s the zona pellucida. It’s homogenous
stained, very brightly stained covering around
the oocyte. That zona pellucida is going to
persist right through until after ovulation.
It’s a very important structure that protects the
oocyte, but also has some very very important
proteins within it. One of them is the attachment
site or the attachment protein for sperm.
When sperm finally get to try to fertilize
the egg, they attach to these proteins on
the surface. And then another component in the
zona pellucida induces the acrosome reaction.
The reaction whereby the sperm can create,
secrete the enzymes required to then penetrate
through the zona pellucida, and then access
the egg to fertilize that egg. It’s a very
prominent structure as you see here. The follicular
theca you see there, the theca folliculi it’s
called, it’s reversed the name sometimes,
that’s the term that you often might see,
and it refers to really the theca interna and
externa layer that I described a few moments
ago. Now, we see a very large mature follicle,
a secondary follicle on the left-hand side.