OOGENESIS

Oogenesis is the process whereby oogonia differentiate into mature oocytes. It starts in the
third month of prenatal development and is finished at the ovulation (ovulation occurs at the puberty
until menopause).
Oogenesis takes place into a specific structure of the ovary: ovarian follicles.
The ovaries are situates into the retro uterine cavum; there is a small depression of the pelvic
wall named ovarian fossa.
In the adult female the ovary is an organ with ovoid form, uncovered by the peritoneum. Each
ovary presents: a thin epithelial layer (externally), cortex and medulla (internal layer).
As the testis, the ovaries have double function: exocrine – the final product is the oocyte;
endocrine – the final products are feminine sexual hormones: estrogen and progesterone. These
functions are realized into a morpho-functional unit = ovarian follicle, which contains the oocyte. The
ovarian follicles are situated in the cortex of the ovary.
Oogenesis has the same phases as the spermatogenesis:
- The multiplication phase
- The growing phase
- The maturation phase.
In the ovary that starts to differentiate (in the third month of prenatal development), the
Primordial germ cells (PGCs) are found into the gonadal cords, which are situated at first in the
medulla, and gradually they appear into the cortex. The germinal cords fragment and form some cells
which surrounded the primordial germ cells. Until the fourth month of prenatal development, PGCs
divide intensive by mitosis and forms 3-4 million of oogonia. These oogonia are arranged in clusters
surrounded by a layer of flat epithelial cells (known as follicular cells, originate from surface
epithelium covering the ovary) forming the first sketch of the ovarian follicle.
Until the seventh month of prenatal development, the majority of oogonia die, remaining
approximately 400 thousands of these cells. They starts the meiotic division but some of them
arrest their cell division in prophase of meiosis I and form primary oocytes. This prophase
may last 40 or more years and finishes only when the cell begins its final
maturation. During this period, it carries 46 double-structured chromosomes. A
primary oocyte, together with its surrounding flat epithelial cells, is known as a primordial
ovarian follicle. The majority of primary oocytes and follicles degenerate and become atretíc
follicle, only 300-400 ovarian follicles continue the development during the sexual maturation
of the female, alternating between the right ovary and the left ovary.

Primordial germ cell -> mitotic division -> Oogonium -> meiotic division -> Primary oocyte in
prophase.

Ovarian cycle
The ovarian cycle represents the morphological changes from the cortex of the
ovary:
- Evolution of the ovarian follicle

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 - Development of the female gamete
- Ovulation
- Formation of corpus luteum
The duration of an ovarian cycle is approximately 28 days; 3 or 4 days more
or less on this period are physiological if the ovarian cycle is regular. The ovarian
cycle starts at puberty until menopause, when the ovarian activity ends, and it is
formed by two components, which are related and concomitant:
a) The follicular cycle: represents the evolution of the ovarian follicle
b) The oogenic cycle: represents the evolution of female gamete

The follicular cycle:

1. The primordial follicle: consists of a primary oocyte surrounded by a single
layer of flattened epithelial cells.
2. Primary follicle: follicular cells become cuboidal and begin to secrete the
zona pellucida, which is visible in irregular patches on the surface of the
oocyte. These cells have an intense metabolic activity.
3. Growing follicle: follicular cells form a stratified layer of granulosa cells
around the oocyte and the presence of a well-defined zona pellucida (a
layer consists of mucopolysaccharides).
4. Cavitary follicle (secundar follicle/ antral follicle): it is characterized by a
cavity full of liquid secreted by the follicular cells, named antrum. Because
of this liquid, the primary oocyte is pushed through periphery of the follicle.
The follicular cells that surrounded the primary oocyte forms corona radiata which is directly
adjacent to the zona pellucida.
The follicular cells that border the antrum forms the granular layer (granulosa cells).
The junction between the granular layer and corona radiate is named cumulus oophorus.
Granulosa cells rest on a basement membrane separating them from surrounding
ovarian
connective tissue (stromal cells) that form the theca folliculi. As follicles continue to
grow, cells of the theca folliculi organize into an inner layer of secretory cells, the theca
interna (produce the ovarian hormones), and an outer fibrous capsule, the theca
externa (has the role to vascularize the follicle).
5. In the 14th day of development, the follicle achieves maximal dimension
and it’s named mature vesicular follicle/ graafian follicle. The antral stage is
the longest, whereas the mature vesicular stage encompasses approximately 37 hours
prior to ovulation.

The Oogenic cycle:

The primary oocyte is formed from the oogonium during the prenatal
development (intrauterine life). Inside the primordial follicle, the primary oocyte
arrests in the prophase of meiosis I. The more ovarian follicles is growing up, the
primary oocyte finish its division.

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 When the secondary follicle is mature, a surge in luteinizing hormone (LH)
induces the preovulatory growth phase. Meiosis I is completed, from the primary oocyte
(diploid cell) resulting in formation of two daughter cells of unequal size, each with 23
double-structured chromosomes (haploid cells). One cell, the secondary oocyte
(haploid cell), receives most of the cytoplasm; the other, the first polar body, receives
practically none. The first polar body lies between the zona pellucida and the cell
membrane of the secondary oocyte in the perivitelline space.

The secondary oocyte then enters meiosis II but arrests in metaphase and it is expelled
from the ovary. Meiosis II is completed only if the oocyte is fertilized; otherwise, the cell
degenerates approximately 24 hours after ovulation. The first polar body may undergo a
second division.

The breaking of the mature follicle and the expelling of the second oocyte is named
ovulation and occurs usually in the 14th day of the ovarian cycle.

In the remaining ovarian cavity after the expelling of the second oocyte, follicular
cells proliferate, develop a yellowish pigment and change into corpus luteum, which
produces the second sexual female hormone – progesterone. If the fertilization does not
occur, in the 27-28th day of the ovarian cycle, the corpus luteum degenerates, because its
activity is not sustained anymore by the pituitary gonadotropins (Follicle-stimulating
hormone = FSH, luteinizing hormone = LH), and forms a mass of fibrotic scar tissue, corpus
albicans. Simultaneously, progesterone production decreases, precipitating menstrual
bleeding. If the oocyte is fertilized, degeneration of the corpus luteum is prevented by
human chorionic gonadotropin, a hormone secreted by the syncytiotrophoblast of the
developing embryo. The corpus luteum continues to grow and forms the corpus luteum of
pregnancy.

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 Summary:

In the female, maturation from primitive germ cell to mature gamete, which is called
oogenesis, begins before birth; in the male, it is called spermatogenesis, and
it begins at puberty. In the female, PGCs form oogonia. After repeated mitotic
divisions, some of these arrest in prophase of meiosis I to form primary oocytes. By the
seventh month, many oogonia have become
atretic, and only primary oocytes remain surrounded by a layer of follicular cells
derived from
the surface epithelium of the ovary. Together, they form the primordial follicle. At
puberty, a pool of growing follicles is recruited and maintained from the finite supply of
primordial follicles. Thus, every month, 15 to 20 follicles begin to grow, and as they mature,
they pass through three stages:

(1) primary or preantral. (2) vesicular or antral, and (3) mature vesicular
or graafian follicle.
The primary oocyte remains in prophase of the first meiotic division until the
secondary follicle is mature. At this point, a surge in luteinizing hormone (LH) stimulates
preovulatory growth: Meiosis I is completed, and secondary oocyte and polar body are
formed. Then, the secondary oocyte is arrested in metaphase of meiosis II approximately 3
hours before ovulation and will not complete this cell division until fertilization.
In the male, primordial cells remain dormant until puberty, and only then do they
differentiate into spermatogonia. These stem cells give rise to primary
spermatocytes, which through two successive meiotic divisions produce four
spermatids. Spermatids go through a series of changes (spermiogenesis) including:

(1) formation of the acrosome; (2) condensation of the nucleus; (3) formation of
neck, middle piece, and tail; and (4) shedding of most of the cytoplasm.

The time required for a spermatogonium to become a mature spermatozoon is

approximately 74 days.

The uterine cycle

The uterine cycle represents all the changes of uterine mucosa influenced by the ovarian hormones.
The uterine mucosa (endometrium) has three layers (from the uterine cavity to the myometrium):
- The compact layer (superficial)
- The spongy layer (intermediate)
- The basal layer (profound)
When the menstrual phase begins, blood escapes from superficial arteries, and
small pieces of stroma and glands break away. During the following 3 or 4 days, the
compact and spongy
layers are expelled from the uterus, and the basal layer is the only part of the endometrium
that is retained. This layer, which is supplied by its own arteries, the basal arteries,
functions as the regenerative layer in the rebuilding of glands and arteries in the
proliferative phase.

Depending on ovarian hormones, the uterine cycle has two phases:

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 1. Pre-ovulatory phase: the estrogens predominate
2. Post-ovulatory phase: the progesterone predominates.

Each one of this phases has several stages.

1. Pre-ovulatory phase:
- Desquamating stage (ischemic stage): it lasts 2-4 days; during this stage, the compact and the
spongy layers are expelled from the uterus together with a variable amount of blood (this
blood can’t be coagulated);
- Regenerative stage: it lasts 4-8 days;
- Proliferative stage: it lasts by the time of ovulation (day 14).
In the last two stages, regeneration and proliferation stage, the uterine mucosa become
thicker. If the maturation of the follicle is quicker than 14 days, the pre-ovulatory phase will
be shorter.

2. Post-ovulatory phase:
- The transformation stage of uterine glands: this glands become spiral and branching; it takes
place during the 15th-19th day of uterine cycle.
- The edema stage of the chorion: between the 20th - 21th day.
- The secretory stage: the uterine glands produce significant amounts of glycogen.
At the same time, the arterioles of uterine mucosa increasing their diameter, become spiral,
thus creating optimal conditions for the implantation of the egg, if the secondary oocyte has been
fertilized. If the fertilization does not occur, the secondary oocyte is eliminate from the uterine
cavity through the uterus.

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