Download Introduction to Embryology Ass. Prof. Dr. Malak A. Al

Introduction to Embryology
Ass. Prof. Dr. Malak A. Al-yawer
This lecture will discuss the following topics :
-Definition of Embryology
-Significance of Embryology
-Old and New Frontiers
-Introduction to Molecular Regulationand Signaling
-Descriptive terms in Embryology
-Mitosis & Meiosis (quick review)
Definition of Embryology
generally refers to prenatal development of embryos and fetuses.
Developmental anatomy
is the field of embryology concerned with the changes that cells, tissues, organs, and the
body as a whole undergo from a germ cell of each parent to the resulting adult. Prenatal
development is more rapid than postnatal development and results in more striking
changes.
SIGNIFICANCE OF EMBRYOLOGY
-Bridges the gap between prenatal development and obstetrics, perinatal medicine,
pediatrics, and clinical anatomy.
-Develops knowledge concerning the beginnings of human life and the changes
occurring during prenatal development.
-Is of practical value in helping to understand the causes of variations in human
structure.
-Illuminates gross anatomy and explains how normal and abnormal relations develop.
Scientific approaches to study embryology have progressed over hundreds of years.
Anatomical approaches
-Experimental embryology
-Grafting experiments
-Molecular approaches
Anatomical approaches dominated early investigations.Observations were made, and
these became more sophisticated with advances in optical equipment and dissection
techniques.
Comparative and evolutionary studies as scientists made comparisons among species
and so began to understand the progression of developmental phenomena.Also
investigated offspring with birth defects, and these were compared to organisms with
normal developmental patterns.
Teratology: Is the study of the embryological origins and causes for birth defects
Experimental embryology
Numerous experiments were devised to trace cells during development to determine
their cell lineages.
-observations of transparent embryos from tunicates that contained pigmented cells
that could be visualized through a microscope.
-vital dyes were used to stain living cells to follow their fates.
-radioactive labels and autoradiographic techniques were employed
-genetic markers (the creation of chick-quail chimeras). In this approach, quail cells,
which have a unique pattern to their heterochromatin distribution around the nucleolus,
were grafted into chick embryos at early stages of development. Later, host embryos
were examined histologically, and the fates of the quail cells were determined.
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development of antibodies specific to quail cell antigens that greatly assisted in the
identification of these cells.
Grafting experiments
provided the first insights into signaling between tissues.
Examples of such experiments included grafting the primitive node from its normal
position on the body axis to another and showing that this structure could induce a
second body axis.
Molecular approaches
Numerous means of identifying cells using reporter genes,fluorescent probes, and
other marking techniques have improved our ability to map cell fates.
other techniques were used to alter gene expression, such as knockout, knock-in, and
antisense technologies has created new ways to produce abnormal development and
allowed the study of a single gene's function in specific tissues.
Molecular biology has opened the doors
-to new ways to study embryology and
- to enhance our understanding of normal and abnormal development.
There are approximately 35,000 genes in the human genome, but these genes code
for approximately 100,000 proteins.
Genes are contained in a complex of DNA and proteins called chromatin.
Each nucleosome consists of an octamer of histone proteins and approximately 140 base
.pairs of DNA.Nucleosomes are joined into clusters by linker DNA and other histone proteins
Chromatin
Heterochromatin:
In inactive state, chromatin appears as beads of nucleosomes on a string of DNA.
Nucleosomes keep the DNA tightly coiled, such that it cannot be transcribed.
Euchromatin:
It is the uncoiled state. DNA must be uncoiled from the beads for transcription to
occur
Induction and Organ Formation
Organs are formed by interactions between cells and tissues. Most often, one group of
cells or tissues causes another set of cells or tissues to change their fate, a process called
Induction. In each such interaction, one cell type or tissue is the inducer that produces a
signal, and one is the responder to that signal.
Competence: Is the capacity to respond to such a signal. It requires activation of the
responding tissue by a competence factor.
Induction- Epithelial mesenchymal interactions
Epithelial cells are joined together in tubes or sheets, whereas mesenchymal cells are
fibroblastic in appearance and dispersed in extracellular matrices
Although an initial signal by the inducer to the responder initiates the inductive event,
cross talk between the two tissues or cell types is essential for differentiation to
continue
Examples of epithelial–mesenchymal interactions include the following:
1. gut endoderm and surrounding mesenchyme produce gut-derived organs, including
the liver and pancreas;
2.limb mesenchyme with overlying ectoderm (epithelium) produce limb outgrowth and
differentiation; and
3.endoderm of the ureteric bud and mesenchyme from the metanephric blastema
produce nephrons in the kidney
Inductive interactions can also occur between two epithelial tissues, such as induction of
the lens by epithelium of the optic cup
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Cell Signaling
Cell-to-cell signaling is essential for
-induction, -conference of competency to respond,
-cross-talk between inducing and responding cells.
Lines of communication are established by:
( 1 ) paracrine interactions, whereby proteins synthesized by one cell diffuse over short
distances to interact with other cells The diffusable proteins responsible for paracrine
signaling are called paracrine factors or growth and differentiation factors (GDFs).
Paracrine factors act by signal transduction pathways either by activating a pathway
directly or by blocking the activity of an inhibitor of a pathway (inhibiting an inhibitor),
Signal transduction pathways include a signaling molecule (the ligand) and a receptor.
The receptor usually spans the cell membrane and is activated by binding with its
specific ligand.
Activation of the receptor is conferred by binding to the ligand. Typically, the activation
is enzymatic involving a tyrosine kinase, although other enzymes may be employed.
Ultimately, kinase activity results in a phosphorylation cascade of several proteins that
activates a transcription factor for regulating gene expression.
2 ) juxtacrine interactions, which do not involve diffusable proteins. Juxtacrine factors
may include products of the extracellular matrix, ligands bound to a cell's surface, and
direct cell-to-cell communications.
Juxtacrine signaling is mediated through signal transduction pathways as well but does
not involve diffusable factors. Instead, there are three ways juxtacrine signaling occurs:
(1) A protein on one cell surface interacts with a receptor on an adjacent cell in a
process analogous to paracrine signaling.
The Notch pathway represents an example of this type of signaling.
2) Ligands in the extracellular matrix secreted by one cell interact with their receptors
on neighboring cells. The extracellular matrix is the milieu in which cells reside. This
milieu consists of large molecules secreted by cells including collagen, proteoglycans
(chondroitin sulfates, hyaluronic acid, etc.), and glycoproteins, such as fibronectin and
laminin.
(3) There is direct transmission of signals from one cell to another by gap junctions.
These junctions occur as channels between cells through which small molecules and ions
can pass. Such communication is important in tightly connected cells like epithelia of the
gut and neural tube because they allow these cells to act in concert.
Mitosis
Is the process whereby one cell divides giving rise to two daughter cells that are
genetically identical to the parent cell . Each daughter cell receives the complete
complement of 46 chromosomes . Mitosis occurs in most somatic cells
Interphase (replication phase) :
Before a cell enters mitosis, each chromosome replicates its deoxyribonucleic acid
(DNA). The chromosomes are extremely long, they are spread diffusely through the
nucleus, and they cannot be recognized with the light microscope.
Prophase
chromosomes are visible as slender threads.The chromosomes begin to coil, contract,
and condense; marking the beginning of prophase. Each chromosome now consists of
two parallel subunits, chromatids , that are joined at a narrow region common to both
called the centromere.
Prometaphase
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only at prometaphase do the chromatids become distinguishable
Metaphase
Chromosomes line up in the equatorial plane and become attached to microtubules
that are extending from centomeres to centrioles forming the mitotic spindle
Anaphase
The centromere of each chromosome divides, marking the beginning of anaphase,
followed by migration of chromatids to opposite poles of the spindle.
Telophase
chromosomes uncoil and lengthen, the nuclear envelope reforms, andthe cytoplasm
divides. Each daughter cell receives half of all doubled chromosome material and thus
maintains the same number of chromosomes as the mother cell.
Meiosis
Is the cell division that takes place in the germ cells to generate male and female
gametes, sperm and egg cells, respectively. The number of chromosomes is halved to
the haploid number and when fertilization takes place the diploid number is restored
Meiosis requires two cell divisions, meiosis I and meiosis II , to reduce the number of
chromosomes to the haploid number of 23
Mitosis and meiosis resemble each other in many respects differing chiefly in the
behavior of the chromosomes during early stages of cell divisions
Stages in the meiotic cycle
Meiosis I
Interphase cell:
diploid ( 2 n ) chromosomes , tetraploid amount of DNA
prophase I ( 5 stages )
1. leptotene : chromosomes initially thin then begin to shorten and thicken
2. zygotene : homologus chromosomes begin to pair point for point .
3. pachytene pairing is complete ,chromosomes still shortening
Metaphase I : chromosome pairs with spindle attachments span equator ; homologus
segments still in contact
Anaphase I : paired chromosomes separate and move towards poles
Telophase I : chromosomes now reduced to haploid ( n) number in each nucleus ;
diploid amount of DNA
Characteristic events during meiosis I
Synapsis : homologus chromosomes align themselves in pairs ( the pairing is exact and
point for point except for the XY combination.
crossover interchange of chromatid segments between paired homologus
chromosomes . Points of interchange are temporarily united and form an x- line
structure ( a chiasma ) . Approximately 1 or 2 crossovers per chromosome with each
meiotic I division and most frequent between genes that are far apart on a chromosome
At the end of meiosis I , two separate cells each with haploid ( n ) number of
chromosomes
Meiosis II
similar to mitosis; the cross over and non cross chromatids separate randomly
At the end of meiosis II , 4 daughter cells chromosome number remaining haploid , DNA
is reduced to the haploid amount
Results of meiotic divisions
1. Genetic variability is enhanced through
Cross over which creates new chromosomes
Random distribution of homologus chromosomesb to daughter cells
2. each germ cell contains a haploid number of chromosomes so that at fertilization the
diploid number of 46 is restored
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A. The primitive female germ cell (primary oocyte) produces only one mature gamete,
the mature oocyte.
B. The primitive male germ cell (primary spermatocyte) produces four spermatids, all of
which develop into spermatozoa.
Clinical correlations
- chromosomal abnormalities
A. numerical ( nondisjunction , translocation )
B. structural
-gene mutations
Nondisjunction
Meiotic nondisjunction
During meiosis ,homologous chromosomes normally pair and then separate .if
separation fails ( nondisjunction )
Non disjunction may involve
-autosomes ( trisomy 21 , trisomy 13 , trisomy 18 )
-sex chromosomes(Klinefelter syndrome (XXY ) 47 chromosomes , XXXY 48
chromosomes ,Turner syndrome (XO )
Mitotic nondisjunction
Nondisjunction may occur during mitosis in an embryonic cell during earliest cell divisions .
Such conditions produce mosaicism . Some cells having an abnormal chromosome number
and others being normal )
Translocation
Sometimes , chromosomes break , and pieces of one chromosome attach to another
Balanced translocation: breakage and reunion occur between two chromosomes but no
genetic material is lost and individuals are normal
Unbalanced translocation: part of one chromosome is lost and an altered phenotype is
produced
Translocation are particularly common between chromosomes 13, 15, 21 and 22
because they cluster during meiosis
Structural abnormalities
Results from chromosomal breakage
Partial deletion of a chromosome e.g. partial deletion of the short arm of chromosome
5 ( Cri-du-chat syndrome
Microdeletions : spanning only a few contiguous genes may result in microdeletion
syndrome or contiguous gene syndrome. e.g. microdeletion on the long arm of
chromosome 15
Gene Mutations
8% of human malformations
A change in the structure or function of a single gene ( single gene mutation )
* Dominant : Affection of one gene of an allelic pair
** Recessive : both allelic gene pairs must be mutant
Gene mutation cause
congenital abnormalities , unborn error of metabolism e.g phenylketone uria , galactosemia
with various degrees of mental retardation.
Next lecture: Gametogenesis
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Gametogenesis
Ass. Prof. Dr. Malak A. Al-yawer
Objectives:
- Talk shortly about primordial germ cells
- Discuss the formation of male gamete
- Discuss the formation of female gamete
- Describe ovarian cycle and ovulation
Gametogenesis( gamete formation): is the process of formation and development of
Of gametes specialized generative cells.
The nomenclature of the developmental stages of gametogenesis is similar in male and
female but the timing of the developmental stages of gametogenesis and the number of
gametes produced are very different in male and female germ cells
Gametogenesisis divided into 4 phases
1. Extra-gonadal origin of primordial germ cells
2. proliferation of germ cells by mitosis
3. meiosis
4. Structural and functional maturation of the ova and spermatozoa
Primordial germ cells
Gametes are derived from primordial germ cells (PGCs) that are formed in the epiblast
during the 2nd week and that move to the wall of the yolk sac.During the 4th week, these
cells begin to migrate by amoeboid movement from the yolk sac toward the developing
gonads, where they arrive by the end of the 5th week
PGCs and Teratomas
are tumors that often contain a variety of tissues, such as bone, hair, muscle, gut epithelia,
and others.It is thought that these tumors arise from
1. pluripotent stem cells that can differentiate into any of the three germ layers or
their derivatives.
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2. Some evidence suggests that PGCs that have strayed from their normal migratory
paths could be responsible for some of these tumors
3. Another source may be epiblast cells that give rise to all three germ layers during
gastrulation
Oogenesis
Maturation of Oocytes Begins before Birth.Once primordial germ cells have arrived in the
gonad of a genetic female, they differentiate into oogonia .Oogonia undergo a number of
mitotic divisions,by the end of the 3rd month, they are arranged in clusters surrounded by a
layer of flat epithelial cells (follicular cells) that originate from surface epithelium covering
the ovary.
The majority of oogonia continue to divide by mitosis, but some of them give rise to
primary oocytes that enter prophase of the first meiotic division.
By the 5th month of prenatal development, the total number of germ cells in the ovary
reaches its maximum(7 million). At this time, cell death begins, and many oogonia as
well as primary oocytes become atretic.
By the 7th month, the majority of oogonia have degenerated except for a few near the
surface. All surviving primary oocytes have entered prophase of meiosis I, and most of
them are individually surrounded by a layer of flat epithelial cells (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
during prophase that is characterized by a lacy network of chromatin .
Primary oocytes remain arrested in prophase and do not finish their first meiotic division
before puberty is reached. This arrested state is produced by oocyte maturation
inhibition (OMI) , a small peptide secreted by follicular cells.
Is the diplotene stage most suitable phase to protect the oocyte against
environmental influences ?
Some oocytes that reach maturity late in life have been dormant in the diplotene stage
of the first meiotic division for 40 years or more before ovulation.
The fact that the risk of having children with chromosomal abnormalities increases with
maternal age indicates that primary oocytes are vulnerable to damage as they age.
The total number of primary oocytes at birth is estimated to vary from 600,000 to
800,000.
During childhood, most oocytes become atretic; only approximately 400,000 are present
by the beginning of puberty, and fewer than 500 will be ovulated.
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Ovarian Cycle
At puberty, the female begins to undergo regular monthly cycles.
Gonadotropin-releasing hormone (GnRH), produced by the hypothalamus, acts on cells
of the anterior pituitary gland, which in turn secrete gonadotropins. These hormones,
follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stimulate and control
cyclic changes in the ovary
At the beginning of each ovarian cycle, 15 to 20 primordial follicles are stimulated to
grow .
Under normal conditions, only one of these follicles reaches full maturity, and the others
degenerate and become atretic.
Most follicles degenerate without ever reaching full maturity.
corpus atreticum: When a follicle becomes atretic, the oocyte and surrounding follicular
cells degenerate and are replaced by connective tissue
primordial follicles when begin to mature, passing through three stages:
(1) primary or preantral
)2 (secondary or antral ,and
(3) preovulatory (Graafian follicle).
The antral stage is the longest, whereas the preovulatory stage encompasses
approximately 37 hours before ovulation
Primordial follicles
Primary oocytes are individually surrounded by a flat epithelial cells ( follicular cells )
Preantral (primary) Follicle
As the primary oocyte begins to grow, surrounding follicular cells change from flat to
and the unit is ,granulosa cuboidal and proliferate to produce a stratified epithelium of
primary follicle called a primary follicle
Granulosa cells rest on a basement membrane separating them from surrounding
ovarian connective tissue (stromal cells) that form the theca folliculi.
Also, granulosa cells and the oocyte secrete a layer of glycoproteins on the surface of the
oocyte, forming the zona pellucida. Small, finger-like processes of the follicular cells
extend across the zona pellucida and interdigitate with microvilli of the plasma membrane
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of the oocyte. These processes are important for transport of materials from follicular
cells to the oocyte.
Secondary(vesicular,antral )follicles
fluid –filled spaces appear between the granulosa cells .coalescence of these spaces
form the antrum. Initially, the antrum is crescent shaped, but with time, it enlarges.It is
surrounded by the theca interna, which is composed of cells having characteristics of
steroid secretion, rich in blood vessels, and the theca externa, outer fibrous layer which
gradually merges with the ovarian connective tissue
Granulosa cells surrounding the oocyte remain intact and form the cumulus oophorus.
At maturity, the secondary follicle may be 25 mm or more in diameter.
Tertiary follicle(preovulatory follicle )
At midcycle, there is an LH surge causes the primary oocyte to complete meiosis I and
the follicle to enter the preovulatory stage (tertiary follicle ) .
meiosis II is also initiated, but the oocyte is arrested in metaphase approximately 3
hours before ovulation.
Maturation of the oocyte
A. Primary oocyte showing the spindle of the first meiotic division.
B. Secondary oocyte and first polar body which lies between the zona pellucida and the
cell membrane of the secondary oocyte in the perivitelline space . The nuclear
membrane is absent.
C. Secondary oocyte showing the spindle of the second meiotic division. The first polar
body is also dividing
Meiosis II is completed only if the oocyte is fertilized; otherwise, the cell degenerates
approximately 24 hours after ovulation. The first polar body also undergoes a second
division
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
1. collagenase activity, resulting in digestion of collagen fibers surrounding the follicle.
2. Prostaglandin levels and cause local muscular contractions in the ovarian wall.
The oocyte, in metaphase of meiosis II, is discharged from the ovary together with a
large number of cumulus oophorus cells. Some of the cumulus oophorus cells then
rearrange themselves around the zona pellucida to form the corona radiate
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During ovulation, some women feel a slight pain “middle pain” because it normally
occurs near the middle of the menstrual cycle.
Ovulation is also generally accompanied by a rise in basal temperature, which can be
monitored to aid couples in becoming pregnant or preventing pregnancy.
Corpus Luteum
After ovulation, granulosa cells remaining in the wall of the ruptured follicle, together
with cells from the theca interna, are vascularized by surrounding vessels.
Under the influence of LH, these cells develop a yellowish pigment and change into
lutean cells, which form the corpus luteum and secrete the hormone progesterone .
Progesterone, together with estrogenic hormones, causes the uterine mucosa to enter
the progestational or secretory stage in preparation for implantation of the embryo.
Fate of the corpus luteum
If fertilization does not occur
the corpus luteum reaches maximum development approximately 9 days after
ovulation. Subsequently, the corpus luteum shrinks because of degeneration of lutean
cells and forms a mass of fibrotic scar tissue, the corpus albicans.
Fate of the corpus luteum
If the oocyte is fertilized
degeneration of the corpus luteum is prevented by human chorionic gonadotropin
(hCG), a hormone secreted by the syncytiotrophoblast of the developing embryo.
The corpus luteum continues to grow and forms the corpus luteum of pregnancy (corpus
luteum graviditatis).
By the end of the third month, this structure may be one third to one half of the total
size of the ovary. Yellowish luteal cells continue to secrete progesterone until the end of
the fourth month; thereafter, they regress slowly as secretion of progesterone by the
trophoblastic component of the placenta becomes adequate for maintenance of
pregnancy. Removal of the corpus luteum of pregnancy before the fourth month usually
leads to abortion.
Spermatogenesis
is the sequence of events by which spermatogonia are transformed into mature
sperms.This maturation process begins at puberty.
It can be divided into 3 phases :
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a. spermatocytosis
b. meiosis
C. spermiogenesis
At birth, germ cells in the male infant can be recognized in the sex cords of the testis as
large, pale cells surrounded by supporting cells .
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 .
Shortly before puberty, the sex cords acquire a lumen and become the seminiferous
tubules
Spermatocytosis
Spermatogonia, which have been dormant in the seminiferous tubules of the testes
since the fetal period, begin to increase in number at puberty.
Spermatogonia proliferate by mitotic division.The newly formed cells can follow one of 2
paths :
1. continue dividing as stem cells - type A spermatogonia
2. they can differentiate during progressive mitotic cycles to become -type B
spermatogonia which are progenitor cells that will differentiate into primary
spermatocytes
Meiosis
2 successive divisions
Meiosis I produce secondary spermatocytes
Meiosis II produce spermatids
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. Thus, the progeny of a single type A
spermatogonium form a clone of germ cells that maintain contact throughout
differentiation. Furthermore, spermatogonia and spermatids remain embedded in deep
recesses of Sertoli cells throughout their development .
In this manner, Sertoli cells support and protect the germ cells, participate in their
nutrition, and assist in the release of mature spermatozoa
Spermatogenesis is regulated by
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LH production by the pituitary gland. LH binds to receptors on Leydig cells and
stimulates testosterone production, which in turn binds to Sertoli cells to promote
spermatogenesis.
Follicle-stimulating hormone (FSH) is also essential because its binding to Sertoli cells
stimulates testicular fluid production and synthesis of intracellular androgen receptor
proteins.
Spermiogenesis
The series of changes resulting in the transformation of spermatids into spermatozoa.
These changes include
(a) formation of the acrosome, which covers half of the nuclear surface and contains
enzymes to assist in penetration of the egg and its surrounding layers during fertilization
;
(b) condensation of the nucleus;
(c) formation of neck, middle piece, and tail; and
(d) shedding of most of the cytoplasm.
In humans, the time required for a spermatogonium to develop into a mature
spermatozoon is approximately 74 days, and approximately 300 million sperm cells are
produced daily.
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
A. Primordial follicle with two oocytes.
B. Trinucleated oocyte.
C. Various types of abnormal spermatozoa.
Next Lecture: the process of fertilization
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Process of fertilization
Ass. Prof. Dr. Malak A. Al-yawer
This lecture will discuss the following topics
1. Approaching of sperm to an oocyte
2. Attaching & penetrating the surface of an ovum by sperm
3. The early changes which follow fertilization
Fertilization
Includes those mechanisms whereby A sperm approaches to Becomes attached to and
then penetrates the surface of an ovum .The early series of changes which follow
Approaching of sperm to an oocyte
Sperm Transport
From their storage site in the epididymis( mainly in its tail) the sperms are rapidly
transported to the urethra by peristaltic contractions of the thick muscular coat of the
ductus deferens.
The accessory sex glands-seminal glands (vesicles), prostate, and bulbourethral glands-•
produce secretions that are added to the sperm-containing fluid in the ductus deferens
and urethra .
The ejaculate:It’s volume averages 3.5 mL, with a range of 2 to 6 mL.
The sperms move 2 to 3 mm per minute, but the speed varies with the pH of the
environment.
They are nonmotile during storage in the epididymis, but become motile in the
ejaculate. They move slowly in the acid environment of the vagina, but move more
rapidly in the alkaline environment of the uterus.
Vagina
200 to 600 million sperms are deposited around the external os of the uterus and in the
fornix of the vagina during sexual intercourse
Cervix
Only 1% of sperm deposited in the vagina enter the cervix, where they may survive for
many hours.
consistency and viscosity of cervical mucus , under hormonal control , play an important
role in the process of fertilization.
Prior to ovulation – watery cervical mucus luteal phase – viscous and disorganized
cervical mucus
Passage of sperms through the uterus and uterine tubes by
-muscular contractions of the uterus and uterine tube. Prostaglandins in the semen are
thought to stimulate uterine motility at the time of intercourse and assist in the movement
of sperms to the site of fertilization in the ampulla of the tube.
-their own propulsion. Fructose, secreted by the seminal glands, is an energy source for the
sperms in the semen.
The trip from cervix to oviduct requires a minimum of 2 to 7 hours
Oviduct
-Uterotubal junction a significant barrier
after reaching the isthmus, sperm become less motile and cease their migration
Spermatozoa are not able to fertilize the oocyte immediately upon arrival in female
genital tract. They must undergo
(1) capacitation and
(2) acrosome reaction to acquire this capability
Capacitation
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It is a period of conditioning in the female reproductive tract , associated with
1.removal of glycoprotein coat and seminal plasma proteins from the plasma
membrane that overlies the acrosomal region of the spermatozoa.
2. reorganization of plasma membrane lipids and proteins to prepare the sperm for
acrosome reaction .
Much of this conditioning occurs in the uterine tube
In the human, it lasts approximately 7 hours .
Sperm can be capacitated by incubation in certain fertilization media.
Oocyte transport
During ovulation, the fimbriated end of the uterine tube becomes closely applied to the
ovary.
The fingerlike processes of the tube, fimbriae, move back and forth over the ovary
It is thought that the oocyte surrounded by some granulosa cells is carried into the tube
by the sweeping action of the fimbriae and fluid currents produced by the cilia of the
mucosal cells of the fimbriae
Once in the tube, cumulus cells withdraw their cytoplasmic processes from the zona
pellucida and lose contact with the oocyte.
-The oocyte passes into the ampulla of the tube, mainly as the result of peristalsis
movements(alternate contraction and relaxation) of the wall of the tube
At ovulation, sperm again become motile, perhaps because of chemoattractants
produced by cumulus cells surrounding the egg, and swim to the ampulla, where
fertilization usually occurs
The fertilizable lifespan of gametes .
The oocyte can be fertilized for up 24 h after ovulation
some sperm cells remain viable in the female reproductive tract for up to 6 days
although most of them have degenerated after 24h
For fertilization to occur successfully, sexual intercourse must, therefore, occur between
5 days before and one day after ovulation
Attaching & penetrating the surface of an ovum by capacitated sperm
1. penetration of the corona radiata
2. penetration of the zona pellucida
3. sperm-oocyte binding
1. Passage of a sperm through the corona radiata.
The corona radiata is a barrier to the sperm cells reaching the oocyte .
The sperm cells are propelled through the loose matrix between the follicular cells of
corona radiata by the action of their flagella.
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.
Only capacitated sperm pass freely through corona cells
2. penetration of the zona pellucida
The zona pellucida is an extracellular membrane , comprised mostly of glycoproteins,
between corona radiata and the oocyte
One particular zona pellucida glcoprotein called zp3 which is species –specific sperm cell
receptor to which molecules on the acrosomal cap of the sperm cell bind .
This binding initiates the acrosomal reaction
The acrosome reaction: Occurs after binding to the zona pellucida,
is induced by zona proteins and culminates in the release of enzymes needed to
penetrate the zona pellucida, including acrosin- and trypsin-like substances
3. Fusion of the Oocyte and Sperm Cell Membranes
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The initial adhesion of sperm to the oocyte is mediated in part by the interaction of
integrins on the oocyte and their ligands, disintegrins, on sperm.
Because the plasma membrane covering the acrosomal head cap disappears during the
acrosome reaction, actual fusion is accomplished between the oocyte membrane and
the membrane that covers the posterior region of the sperm head.
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.
Polyspermy
penetration of more than one spermatozoon into the oocyte
Prevention of polyspermy
- Fast block to polyspermy
-Slow block to poly spermy
Fast block to polyspermy
Once the first sperm cell attaches to the integrin (alpha 6 beta 1) on the surface of the
oocyte plasma membrane, depolarization of the oocyte plasma membrane occurs
within 2-3 seconds.
This depolarization( fast block to poly spermy) prevents additional sperm from attaching
to the oocyte plasma membrane
Slow block to poly spermy
Depolarization causes the intracellular release of ca+2 , which in turn causes the
exocytosis of water and other molecules from secretory vesicles referred to as cortical
granules on the inner surface of the oocyte plasma membrane
The released fluid causes the oocyte to shrink and the zona pellucida to denature and
expand away from the oocyte .
As a result of denaturation of the zona pellucida , zp3 is inactivated and no additional
sperm cells can attach . This reaction is referred to as the slow block to poly spermy
The early series of changes which follow “ egg activation “
Prior to fertilization , the egg is in a quiescent state . Upon binding of a sperm ,the egg
rapidly undergoes a number of metabolic and physical changes collectively called “ egg
activation “
- Cortical and zona reactions
- Resumption of the second meiotic division
- Metabolic activation of the egg –The activating factor is probably carried by the
spermatozoon.
The main results of fertilization
-Restoration of the diploid number of chromosomes, , the zygote contains a new
combination of chromosomes different from both parents.
• Determination of the sex of the new individual. An X-carrying sperm produces a female
(XX) embryo, and a Y-carrying sperm produces a male (XY) embryo. Hence, the
chromosomal sex of the embryo is determined at fertilization.
• Initiation of cleavage.
Clinical correlates
Contraception
Barrier techniques of contraception include
the male condom, and the female condom,the diaphragm, the cervical cap, and
the contraceptive sponge
Prevention of ovulation
The contraceptive pillis a combination of estrogen and the progesterone which together
inhibit ovulation but permit menstruation.
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Depo-Provera is a progestin compound that can be implanted subdermally or injected
intramuscularly to prevent ovulation for up to 5 years or 23 months.
A male “pill”
has been developed and tested in clinical trials.It contains a synthetic androgen that
prevents both LH and FSH secretion
It either stops sperm production (70% to 90% of men) or reduces it to a level of
infertility.
The intrauterine device (IUD)
is placed in the uterine cavity. Its mechanism for preventing pregnancy is not clear but
may entail direct effects on sperm and oocytes or inhibition of preimplantation stages of
development.
Vasectomy and tubal ligation
are effective means of contraception, and both procedures are reversible, although not
in every case.
Infertility
Infertility is a problem for 15% to 30% of couples.
Male infertility
may be a result of insufficient numbers of sperm and/or poor motility.
Infertility in a woman
occluded uterine tubes (most commonly caused by pelvic inflammatory disease),
hostile cervical mucus,
immunity to spermatozoa,
absence of ovulation, and others.
Assisted reproductive technology (ART)
is a group of fertility treatments that involve both the sperm and the egg.
-In vitro fertilization (IVF),-intracytoplasmic sperm injection (ICSI)
-gamete intrafallopian transfer (GIFT),zygote intrafallopian transfer (ZIFT).
In vitro fertilization (IVF)
is the most common type of ART.
the sperm fertilizes the egg outside the body, and doctors implant it into the woman's
uterus in hopes of a successful pregnancy. IVF cycle takes four to six weeks to complete
and usually costs about $12,000
The risk of producing malformed offspring by in vitro procedures is low because
preimplantation-stage embryos are resistant to teratogenic insult,
A disadvantage of IVF is its low success rate
only 20% of fertilized ova implant and develop to term. Therefore, to increase chances
of a successful pregnancy, four or five ova are collected, fertilized, and placed in the
uterus. This approach sometimes leads to multiple births
The following methods of ART require patent uterine tubes.
Gamete intrafallopian transfer (GIFT)
introduces oocytes and sperm into the ampulla of the fallopian (uterine) tube,
where fertilization takes place.
zygote intrafallopian transfer (ZIFT)
fertilized oocytes are placed in the ampullary region.
Intracytoplasmic sperm injection ICSI)
(oligozoospermia) or even (azoospermia), can be overcome by using intracytoplasmic s
perm injection (ICSI).
With this technique, a single sperm, which may be obtained from any point in the male
reproductive tract, is injected into the cytoplasm of the egg to cause fertilization.
The technique carries an increased risk for fetuses to have Y chromosome deletions but
no other chromosomal abnormalities.
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