GENERAL EMBRIOLOGY

GAMETOGENESIS
The beginning of life: development begins with fertilization, the process by which the
male gamete, the sperm, and the femalegamete,theoocyte,unitetogiverisetoazygote.Two highly specialised sexual haploid cells fuse and give rise to another diploid one
whith an unique dna.
Where do gametes come from?
Gametes are derived from primordial germ cells (PGCs). These are diploid cells
capable of differenciating. In contrast, somatic cells are the ones found in the
rest of the body and are uncapable of differenciating , although they are diploid
too.

Origin and migration of PGC

PGC are formed in the epiblast during the second week and that move to the
wall of the yolk sac ( initially intended to feed the embryo). During the fourth
week these cells begin to migrate from the yolk sac toward the developing
gonads, where they arrive by the end of the fth week. Mitotic divisions
increase their number during their migration and also when they arrive in the
gonad. In preparation for fertilization, germ cells undergo
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Gametogenesis: which includes meiosis, to reduce the number of

chromosomes

Cytodifferentiation: to complete their maturation.

Reduction of genetic information --- Meiosis

Consequences : genetical variability + reduction genetic information

Teratomas are tumors of disputed origin that often contain a variety of tissues,
such as bone, hair, muscle, gut epithelia, and others. It is thought that these
tumors arise from a pluripotent stem cell that can differentiate into any of the
three germ layers or their derivatives.

Abnormal divisions : Abnormalities in chromosome number may originate

during meiotic or mitotic divisions

In meiosis, two members of a pair of homologous chromosomes normally

separate during the rst meiotic division so that each daughter cell receives
one member of each pair .Sometimes, however, separation does not occur
and is called nondisjunction.This occurs during either the rst or the second
meiotic division of the germ cells. As a result of nondisjunction of the
chromosomes, one cell receives 24 chromosomes, and the other receives
22 instead of the normal 23.

Mitotic nondisjunctionin an embryonic cell during the earliest cell divisions.

Such conditions produce mosaicism, with some cells having an abnormal
chromosome number and others being normal. Affected individuals may

exhibit few or many of the characteristics of a particular syndrome,

depending on the number of cells involved and their distribution.

SPERMATOGENESIS
Consists on the formation of male gametes / sperm from the PGC.
5th week
PGC reach the male gonad which is still in an early stage of life.

Birth
PCG in the male can be recognized in the sex cords of the testis as large, pale
cells surrounded by supporting cells which are derived from the surface
epithelium of the gland in the same manner as follicular cells, become
sustentacular cells, or Sertoli cells. They keep resting until puberty.

Puberty
The sex cords develop into the seminiferous tubules due to light. At about the
same time, primordial germ cells give rise to spermatogonial stem cells.

At regular intervals, cells emerge from this stem cell population to form type A
spermatogonia, and their production marks the initiation of spermatogenesis.

Type A Spermatogonia

limited number of mitotic divisions

last cell division

Type B spermatogonia
1 generation goes through mitosis

Primary spermatocytes 46 XY
enter a prolongued prophase (22 days)
completion of meiosis I.

-------------------------------------------------------------------------------Secondary spermatocytes.
23 double chromosomes
Meiosis II

Spermatids
23 single chromosomes

Throughout this series of events, from the time type A cells leave the stem cell
population to formation of spermatids, cytokinesis is incomplete, so that
successive cell generations are joined by cytoplasmic bridges. They are
produced in waves.
Spermiogenesis ( 64 days)
The spermatids are inmmature sperms that must undergo morphological
changes to become functional. Thesechangesinclude

Formationoftheacrosome, which covers half of the nuclear surface and

contains enzymes to assist in penetration of the egg and its surrounding
layers during fertilization

condensation of the nucleus

formation of neck, middle piece, and tail

shedding of most of the cytoplasm residual bodies

Motion
When fully formed, spermatozoa enter the lumen of seminiferous tubules.
From there, they are pushed toward the epididymis by contractile elements in
the wall of the seminiferous tubules.Although initially only slightly motile,
spermatozoa obtain full motility in the epididymis.

Abnormal gametes
Abnormal spermatozoa are seen frequently, and up to 10% of all spermatozoa
have observable defects. The head or the tail may be abnormal; spermatozoa
may be giants or dwarfs; and sometimes they are joined.

OOGENESIS
5th week
Once primordial germ cells have arrived in the female gonad (ovary) they
differentiate into oogonia 2N2C.

First months - End 3rd month

These cells experiment mitosis massively
Arranged in clusters surrounded by a layer of at epitelial ( follicullar cells)
forming clusters.

Next months
The majority of oogonia continue to divide by mitosis, but some of them arrest
their cell division in prophase of meiosis I and form primary oocytes 2N4C
During the next few months ,oogonia increase rapidly in number

 Fifth month of prenatal development

The total number of germ cells in the ovary reaches its maximum, estimated at
7 million. At this time, cell death begins, and many oogonia as well as primary
oocytes become atretic.

Seventhmonththemajorityofoogoniahavedegeneratedexcept.Allsurvivingprima
ryoocyteshaveenteredprophase of meiosis I, and most of them are individually
surrounded by a layer of at epitelial
cells.Aprimaryoocyte,togetherwithitssurroundingat epithelial cells, is known
as a primordial follicle.

Near the time of birth

All primary oocytes have started prophase of meiosis I, but instead of
proceeding into metaphase, they enter the diplotene stage, a resting stage.
Primary oocytes remain in prophase and do not nish their rst meiotic division
before puberty is reached, apparently because of oocytematurationinhibitor
(OMI)

During childhood
Most oocytes become atretic; only approximately 400,000 are present by the
beginning of puberty, and fewer than 500 will be ovulated

Puberty
Each month, 15 to 20 follicles selected from this pool begin to mature, passing
through three stages:

1. As the primordial follicle is stimulated by FSH , surrounding follicular cells

change from at to cuboidal
andproliferatetoproducestratiedepitheliumofgranulosa cells now is called
a primary follicle2N4C

Granulosa cells rest on a basementmembraneseparatingthemfromthe

ovarythatformthe theca folliculi. As follicles continue to grow, cells of the
theca folliculi organize into an inner layer of secretory cells, the theca
interna, and an outer brous capsule, the theca externa.

Also, granulosa cells and the oocyte secrete a layer of glycoproteins on the
surface of the oocyte, forming the zona pellucida.

Small, nger-like processes of the follicular cells extend across and provide
blood and oxygen.

2. Fluid-lled spaces appear between granulosa cells. Coalescence of these

spaces forms the antrum, and the follicle is termed a secondary (vesicular,
Graaan) follicle. 2N4C
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Granulosa cells surrounding the oocyte remain intact and form the cumulus
oophorus.

3. Tertiary follicle or Graaf follicle

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With each ovarian cycle, a number of follicles begin to develop, but usually
only one reaches full maturity. The others degenerate and become atretic.

When the secondary follicle is mature, a surge in luteinizing hormone (LH)

induces the preovulatory growth phase. Meiosis I is completed,
resultinginformationoftwodaughtercellsofunequalsize,eachwith23doublestr
uctured chromosomes. 1N2C
the secondary oocyte, receives most of the cytoplasm
the rst polar body, receives practically none. It lies between the
zona pellucida and the cell membrane of the secondary oocyte in
the perivitelline space.

4. The cell then enters meiosis II but arrests in metaphase approximately 3

hours before ovulation. Meiosis II is completed only if the oocyte is
fertilized; otherwise, the cell degenerates approximately 24 hours after
ovulation.

Abnormalities
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Follicles with 2 oocytes

Oocytes with 3 nucleus

THE OVARIAN CYCLE

Aproximate duration : 28 days

1st phase : Menstruation gets rid previous layer

 The follicular or proliferative phase (5-14)

At puberty, the female begins to undergo regular monthly cycles. These sexual cycles
are controlled by the hypothalamus. Gonadotropin-releasing hormone (GnRH)
produced by the hypothalamus acts on cells of the anterior pituitary gland, which in
turn secrete gonadotropins.
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The hormone is not necessary to promote development of primordial

follicles to the primary follicle stage, but without it, these primary follicles
die and become atretic.

Follicular cells then grow and continue meiosis I.

In cooperation, granulosa and thecal cells produce estrogens that:

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cause the uterine endometrium to enter the follicular or proliferative

phase

cause thinning of the cervical mucus to allow passage of sperm

stimulate the pituitary gland to secrete LH.

Mid-cycle ( Around day 14)

At mid-cycle, there is an LH surgeand an increase in FSH caused by an increase
in strogens act in the hypophysis that
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elevates concentrations of maturation-promoting factor, causing oocytes

to complete meiosis I and initiate meiosis II

Stimulates production of progesterone by follicular stromal cells

(luteinization)

causes follicular rupture :Meiosis II is also initiated, but the oocyte is

arrested in metaphase approximately 3 hours before ovulation. In the
meantime, the surface of the ovary begins to bulge locally, and at the apex,
an avascular spot, the stigma, appears. The high concentration of LH
increases collagenase activity, resulting in digestion of collagen bers
surrounding the follicle. Prostaglandin levels also increase in response to
the LH surge and cause local muscular contractions in the ovarian Wall
which extrude the oocyte, which together with its surrounding granulosa
cells from the region of the cumulusoophorus, breaks free (ovulation) and
oats out of the ovary .Some of the cumulus oophorus cells then rearrange
themselves around the zona pellucida to form the corona radiata.

After ovulation, granulosa cells remaining in the wall of the ruptured

follicle, under the inuence of LH, develop a yellowish pigment and change
into lutean cells, which form the corpus luteum and secrete the hormone

progesteronewhich causes the uterine mucosa to enter the progestational

or secretory stage in preparation for implantation of the embryo.

Ooccyte transport
It is carried into the tube by these sweeping movements of the mbriae and by
motion of cilia on the epithelial lining. Once in the tube, cumulus cells withdraw
their cytoplasmic processes from the zona pellucida and lose contact with
theoocyte. Once the oocyte is in the uterine tube, it is propelled by cilia with
the rate of transport regulated by the endocrine status during and after
ovulation.

Secretory or lutheinic phase (14-28)

Progesterone finalices the necessary endometrium preparation in order to the
embryo in case of fecundation. The rise of progesterone in blood causes a rise
in the basal temperatura of the womans body.

No fertilization
If fertilization does not occur, the corpus luteum reaches maximum
developmentapproximately 9 days after ovulation. It can easily be recognized
as a yellowish projection on the surface of the ovary. Subsequently, the corpus
luteum shrinks because of degeneration of lutean cells and forms a mass of
brotic scar tissue, the corpus albicans. Simultaneously, progesterone
production decreases, precipitating menstrual bleeding.

Fertilization
Degeneration of the corpus luteum is prevented by human chorionic
gonadotropin (hCG).The corpus luteum continues to grow and forms the corpus
luteum of pregnancy (corpus luteum graviditatis). Yellowish luteal cells
continue to secrete progesterone until the end of the fourth month;
thereafter,theyregressslowly assecretionofprogesterone byte trophoblastic
component of the placenta becomes adequate for maintenance of pregnancy.

FERTILIZATION
Fertilization,theprocessbywhichmaleandfemalegametesfuse,occursinthe ampullary
region of the uterine tube ( trompa de Falopio).
Spermatozoid are deposited in the vagina during the coitus. Spermatozoids are in a
fluid mdium, either semen or sperm, which have a basic pH, while the womans
vagina has an acid pH. The semen makes the pH rise and this allows the spermatozoa
travel to the uterine tuve where the ooctyte is. Spermatozoa quickly travel from the
vagina to the utherus and then to the utherine tube thaks to contractions of the
muscular layers from the utherus and the tube .However, spermatozoa are not able to
fertilize the oocyte immediately upon arrival in the female genital tract but must
undergo
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Capacitation: is a period of conditioning in the female reproductive tract

that in the human lasts approximately 7 hourswhich occurs in the uterine
tube, entails epithelial interactions between the sperm and mucosal surface
of the tuve in which glycoprotein coat and seminal plasma proteins are
removed from the plasma membrane that overlies the acrosomal region of
the spermatozoa

The acrosome reaction :release ofenzymes needed to penetrate the zona

pellucida, including acrosin and trypsin-like substances, which occurs after
binding to the zona pellucida.

1. Phase 1: penetration of the corona radiata

Of the 200 to 300 million spermatozoa deposited in the female genital tract,
only 300 to 500 reach the site of fertilization. Only one of these fertilizes the
egg.

2. Phase 2: penetration of the zona pellucida

Both binding and the acrosome reaction are mediated by the ligand ZP3.

Release of acrosomal enzymes (acrosin) allows sperm to penetrate the zona,

thereby coming in contact with the plasma membrane of the oocyte.

3. Phase 3: fusion of the oocyte and sperm cell membranes

In the human, both the head and tail of the spermatozoon enter the cytoplasm
of the oocyte,but the plasma membrane is left behind on the oocyte surface.

Cortical and zona reactions.Asaresultofthe releaselysosomal enzymes, the

oocyte membrane becomes impenetrable to other spermatozoa, and the
zona pellucida alters its structure and composition to prevent sperm
binding and penetration. These reactions prevent polyspermy (penetration
of more than one spermatozoon into the oocyte).

Resumptionofthesecondmeiotic division
the second polar body: receives hardly any cytoplasm
other daughter cell is the denitive oocyte. Its chromosomes (22+X)
arrange themselves in a vesicular nucleus known as the female
pronucleus.
The spermatozoon, meanwhile, moves forward until it lies close to the
female pronucleus. Its nucleus becomes swollen and forms the male
pronucleus , the tail detaches and degenerates. Morphologically, the
male and female pronuclei are indistinguishable.Each pronucleus must
replicate its DNA. If it does not, each cell of the two-cell zygote has only
half of the normal amount of DNA.

The main results of fertilization

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Restoration of the diploid number of chromosomes, half from the father

and half from the mother.

Determination of the sex of the new individual. An X-carrying sperm

producesafemale(XX)embryo,andaY-carryingspermproducesamale (XY)
embryo. Hence, the chromosomal sex of the embryo is determined at
fertilization.

Zygote + Initiation of cleavage.

Uterus at Time of Implantation

The wall of the uterus consists of three layers:
1. endometrium or mucosa lining the inside Wall
2. myometrium, a thick layer of smooth muscle; and
3. perimetrium, the peritoneal covering lining the outside wall
During this menstrual cycle, the uterine endometrium passes through three stages
1. The proliferative phasebeginsattheendofthemenstrualphase,isunder the
inuence of estrogen, and parallels growth of the ovarian follicles.
2. The secretory phase begins approximately 2 to 3 days after ovulation in
response to progesterone produced by the corpus luteum.
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If fertilization does not occur, shedding of the endometrium (compact and

spongy layers) marks the beginningofthemenstrualphase.

Iffertilizationdoesoccur,theendometriumassists in implantation and

contributes to formation of the placenta.

3. At the time of implantation, the mucosa of the uterus is in the secretory

phaseduring which time uterine glands and arteries become coiled and the

tissue becomes succulent. As a result, three distinct layers can be recognized in

the endometrium: a supercial compact layer, an intermediate spongy layer,
and a thin basal layer.Normally, the human blastocyst implants in the
endometrium along the anterior or posterior wall of the body of the uterus,
where it becomes embedded between the openings of the glands . If the
oocyte is not fertilized, venules and sinusoidal spaces gradually become packed
with blood cells, and an extensive diapedesis of blood into the tissue is seen.
4. When the menstrual phase begins, blood escapes from supercial 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