Primordial germ cells multiply during fetal development.

At birth, the ovary contains around 400

000 primordial follicles which contain primary oocytes. These primary oocytes do not undergo
further mitotic division, and they remain arrested in the prophase stage of meiotic division I,
until sexual maturity (see Meiosis, in the topic cell). Compare this to male gametogenesis.

At sexual maturity, two hormones, produced by the pituitary gland: follicle stimulating hormone
(FSH) and lutenising hormone (LH) cause these primordial follicles to develop. In each ovarian
cycle, about 20 primordial follicles are activated to begin maturation. however, normally only
one follicle fully matures, and the rest contribute to the endocrine function of the ovary.

When activated, the first meiotic division is completed. When this happens, the primary follicle
has matured into a secondary follicle. The second division then starts, and a Graafian follicle is
formed. This contains a secondary oocyte. This second division is not completed, unless the
ovum is fertilised.

Meiosis

This diagram shows how primary oocytes in the primordial follicles are diploid, and are starting
their first meiotic division. The pairs of homologous chromosomes (one maternal, one paternal)
pair up on the spindle, and genetic material can be swapped over. Even the X and Y chromosome
(if present) will pair up, and form a partial bivalent.

At completion of first meiotic division: one of the chromosome pairs is segregated to each of
the daughter cells. For example, if there is an XY pairing, then one cell will receive the X, and
one the Y chromosome pair.Thus when this division is completed, the resulting secondary
oocyte has 'diploid' DNA, but the chromosome copies are only derived from one of the original
chromosomes in the parent cell. (i.e. either maternal or paternal). These cells are called 'haploid'.
One of the daughter cells degenerates and forms a 'polar body'. These are small and degenerate
rapidly.
At completion of the second meiotic division: this division occurs without the DNA being
replicated prior to division. Each daughter cell receives one chromatid from the original
chromosome pair to form the gamete producing cells that only have a single copy of each
chromosome. Again one of the daughter cells forms a polar body.

Thus only one gamete is formed from one primary oocyte (compare this to male gametogenesis).

For more information compare normal mitotic division with meiotic division.

Hormonal changes during the menstrual cycle

Development of the follicles is stimulated by production of follicle stimulating hormone (FSH)

by the pituitary gland. Ripening of the follicles then results in an increase in oestrogen levels, as
oestrogen is secreted by follicular cells. This increase in oestrogen levels feeds back to the
pituitary, and suppresses further release of FSH (negative feedback). The follicles also release a
second hormone called inhibin, which also suppresses further production of FHS. As the
oestrogen levels rise, this triggers a a mid cycle surge in a second pituitary hormone
called Lutenising hormone (LH), which causes the follicle to rupture (ovulation). LH also
causes ruptured follicles to lutenise, forming a transitory endocrine organ called the corpus
luteum. This looks yellow, due to its pigmented lutein cells (luteus is latin for yellow). The
corpus lutein secretes progesterone and oestrogen. The progesterone levels feed back to the
pituitary and suppress further release of LH. If fertilisation does not occur, the corpus luteum
degenerates into a small white fibrous scar called the corpus albicans. The resulting decline
in progesterone (and to some extent oestrogen) levels precipitate menstruation. The decline in
oestrogen levels, feeds back to the pituitary and there is a corresponding increase in FSH to
being the cycle all over again.

Ovarian follicles

Primordial follicle

Primordial germ cells migrate into the developing gonad early in embryogenesis, and
differentiate into oogonia. These oogonia proliferate by mitosis. Some of these enlarge and
develop into larger cells called primary oocytes and enter the first meiotic division on the
pathway to making gametes by meiosis. This happens between 3 and 8 months of gestation in the
human embryo.

These 'primary' oocytes become arrested in prophase of the first meiotic division until the female
becomes sexually mature.

At sexual maturity, a small number of primary oocytes (20-50) mature each month and complete
the fist meiotic division to become secondary oocytes, under the influence of follicle stimulating
hormone. The oocytes synthesise a coat and cortical granules - this glycoprotein coat is called
the 'zona pellucida'. They also accumulate ribosomes, yolk, glycogen, lipid and the mRNA that
will be used later on after fertilisation to direct early development of the embryo.

After a second mitotic division, ova are formed.

In primordial follicles, the oocyte is arrested in the last stage of prophase (known as dictyotene).
At this stage, it is surrounded by a single layer of flattened ovarian follicular epithelial cells.
(These cells are also known as granulosa cells).

They are small, and usually found close to the outer edge of the cortex.

Primary follicle
When the primordial follicle is stimulated, it becomes a primary follicle. The oocyte enlarges,
and the follicular cells divide. A follicle that has two layers of follicular cells is called a primary
follicle. These cells continue to hypertrophy and proliferate to form many layers surrounding the
oocyte. Eventually these cells become known as 'granulosa' cells. The granulosa cells will secrete
progesterone after ovulation.

A thick glycoprotein layer develops between the oocyte and the zona granulosa, called the zona
pellucida.

Finally, the stroma around the follicle develops to form a capsule like 'theca'. (Theca is greek for
'box'). Only one of the maturing follicles completes the maturation process each month. The rest
degenerate into atretic follicles. Follicular maturation takes about 3 months.

Secondary Follicle

The primary follicle develops into a secondary follicle.The secondary follicles look very similar
to primary follicles, except that they are larger, there are more follicular cells, and there are small
accumulations of fluid in the intracellular spaces called follicular fluid (nutritive fluid for the
oocyte). These gradually coalesce to form an antrum.

The surrounding granulosa cells is called the cumulus oophorus (greek for 'egg bearing heap').

The surrounding theca differentiates into two layers: the Theca interna (rounded cells that
secrete androgens and follicular fluid) and a more fibrous Theca externa - spindle shaped cells.
The androgens are converted into oestrogen by the granulosa cells.
Graffian follicle.

The secondary follicle develops into a Graffian follicle.

The first meiotic division is now completed, and the oocyte is now a secondary oocyte, and starts
its second meiotic division. After the first meiotic division, most of the cytoplasm goes into one
of the two daughter cells. The other becomes the polar body (hard to see).

The folicular fluid fills a single space, called the antrum, which is surrounded by the follicular
cells - called the membrana granulosa. The granulosa cells that surround the oocyte, and
project into the antrum are called as the cumulus oophorus. There is a basement membrane
between the granulosa cells and the theca interna. The fibrous theca externa merges with the
surrounding stroma.

The oocyte, zona pellucida and the follicular cells surrounding the ooctye (known as the corona
radiata) are all expelled at ovulation, and enter the fallopian tube.

Once released, the oocyte begins its second meiotic division, as far as metaphase II. Division
only carries on if the ovum is fertilised.

Corpus Luteum

After ovulation, the ruptured follicle collapses and fills with a blood clot (corpus
haemorrhagicum) which then forms the corpus luteum. The granulosa cells enlarge, and become
vesicular, and are now called the granulosa lutein cells. these become folded, as you can see
here.

The spaces between the folds are filled with theca interna cells, which also enlarge and
become glandular, and are now known as the theca lutein cells.

The zona granulosa cells begin to secrete progesterone (granulosa lutein cells). The corpus
luteum also secretes oestrogen (which inhibits FSH) and relaxin (which relaxed the fibrocartilage
of the pubic symphysis).

If pregnancy does not occur, then the corpus luteum degenerates into the corpus albicans, and
levels of oestrogen and progesterone fall, allowing release of FSH and LH.

If pregnancy does occur, then the syncytiotrophoblasts of the placenta release human chorionic
gonadotrophin, and the corpus luteum persists.

About 20 primordial follicles start developing in each cycle, but only ONE makes it!

This image shows a corpus luteum in a human ovary. (from anatomy.iupui.edu) It takes up one
third of the ovary.
Corpus albicans

This image shows an atretic corpus luteum or corpus albicans. The cellular elements have
degenerated, and macrophages phagocytose the dead cells. Fibrous tissue is left behind. The
corpus albicans looks pale. It will continue to shrink, eventually forming a small scar on the side
of the ovary.