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Lecture 3
ESS_2nd semester
Embryology - definition, the object and significance of embryology
Phases of the human ontogeny
Gametes - their structure, physiology and origin
(gametogenesis). Differences between spermatogenesis
and oogenesis
Transportation of gametes. Sperm capacitation and acrosome
reaction
Fertilization and cleavage, the morula and blastocyst
Implantation
development of plant as well as animal organisms begins when an ovum is
fertilized and ends at the moment of the death of individual
the time period from fertilization to death is called as the ontogeny
(also as life cycle)
in placental mammals, including the human, ontogeny divides 2 periods of
different length:
prenatal period (prenatal development) - from fertilization of an
ovum to delivery of fetus
postnatal period (postnatal development) - from the delivery to
death of the individual
in mammals, goal of embryology consists first of all in study and
description of events occuring during the prenatal period (phase) of
development
similar goals and orientation has also medical embryology: to describe
and explain events and processes from the fertilization to the
birth of the human
Significance of embryology
the basic theoretical medical branch
good knowledge of embryology is important in many medical disciplines:
anatomy - knowledge of the human development helps to understand
complicated relationships between many organs of the human body
embryology shows more closely relationships and bounds to anatomy than
to histology (reasons for teaching of embryology together with histology are
rather practical then logical as study of the pre-embryonic and early
embryonic stages needs to use and studied only with the use of histological
slides)
pathology - knowledge of embryology is explored namely in study of
restorative (healing) processes and in description and classification of
neoplasms (tumours)
obstetrics, pediatrics and surgery - knowledge of normal development is
essential to understanding the mechanisms, symptomatology and correction
of congenital malformations
a special medical line -prenatal medicine- was constituted in last years, it
deals with diagnosis, treatment and prevention of congenital malformations
Phases of prenatal development in the human
pre-embryonic phase
involves the first 3 weeks from fertilization of the ovum
several well-defined stages are distinguished :
- zygote (fertilized ovum) = the cell standing at the beginning of development
of a human being; there is a result of a fusion of the male and female sex cells or
gametes
- morula (from latin morus – mulberry) =
the solid ball consisting of 12 to 16 blastomeres
blastomeres = cells that result in process of cleavage
of the zygote, blastomeres are genetic equal and
they do not substantially differ each other,
prospective properties or developmental potency
of blastomeres are the same, each of them can
give rise to a new individuum
- blastocyst = the stage with a cavity inside that is filled with fluid, 2 different
cell populations differentiate at the first time in development: trophoblast cells +
inner cell mass or embryoblast cells, during the day 5
- gastrula = the bilaminar pre-embryonic stage, in which the main body
axis and polarity begin to become apparent, the bilaminar stage develops
on day 7 and lasts to the end of the second week after fertilization
embryonic phase
lasts from the beginning of the 4th week to the end of the 8th week
in the phase anlages of the all body organs are constituted
by the end of it, the embryo is recognizable human in appearance and
measures cca 2-3 cm from head to tail
fetal phase
it lasts from the 9 week to delivery of fetus;
during the fetal phase, development of organs rapidly continue, some of them
enter their function, the fetus grows quickly in length and increases its weight
gain, in particular during the terminal months
Phases of the postnatal development in the human
infancy – from the birth to the end of the first year of the age (the first
two weeks of infancy are called as the newborn or neonatal period)
childhood - from 13 month until 12 to 13 years; the primary teeth
appear and are replaced by the secondary or permanent teeth
puberty - is the period between 12-15 years in girls and 13-16 years in
boys, during which secondary sexual characteristics develop
adolescence - follows the puberty and ends 3-4 years after it; the
organism reaches sexual but also physical, mental and emotional maturity
adulthood - a period in which developmental changes occur very slowly
and are mostly characterized by selective loss of highly specialized cells and
tissues
postnatal development of the human is studied and treated with various
medical branches
Structure and origin of gametes
gametes = generative (germ or sex) cells
in comparison with somatic cells, gametes are highly specialized and contain only half the usual number of
chromosomes
the sperm or spermatozoon (the male germ cell)
the ovum or egg cell (the female germ cell)
human gametes similar to gametes of another species substantially differ each other in size, structure,
motility, and viability
The sperm, spermatozoon
is a motile cell that is cca 60 m long
a head, a neck (connecting piece) and a tail
the head has a flattened pyriform shape , approximately 4 m in length, consists of the sperm
plasma membrane, condensed nucleus and acrosomal cap covering the anterior two-thirds of the nucleus
the acrosomal cap derives from the Golgi apparatus and contains hydrolytic enzymes (hyaluronidase, acrosin,
neuraminidase)
the neck (= connecting piece) is very short sperm section composed of segmented columns,
proximal centriole, and a part of distal centriole that serves as basal body of the axoneme of tail
the tail - cca 55 m in length
middle piece –
about 5 to 9 m in length,
1-2 m in diameter, consists of
the axoneme that is inserted
in the distal centriole located
in the neck,
is surrounded by 9 outer
dense fibers
(dense columns) and externally
to them by
a mitochondrial sheath
principal piece - 40-45 m in length
is narrower than the middle piece
contains the axoneme, 9 outer dense
fibers and fibrous sheath
end piece
cca 5-10 m in length, consists of the axoneme
and associated cytoplasm only
the neck and all pieces of the tail are covered with a membrane that is continuous with the
plasma membrane of the head
the semen (ejaculate)
viscid fluid expelled from the
urethra during the orgasm
volume of one ejaculate is 3 - 6 ml
it consists of
the seminal plasma =
secretions of accessory sex glands
(seminal vesicles and prostate)
formed elements:
spermatozoa, exfoliated epithelial
cells form genital and urinary
passages, lymfocytes, prostatic
concretions
average sperm density 60 - 100
million/ml - normospermy
(density lesser than 20 million/ml =
infertility)
average sperm velocity is 2 - 3
mm/min under alkaline pH
spermatozoa retain ability to
fertilize ovum not longer than 16 to
24 hours
The ovum
a large spherical nonmotile cell with diameter of over 100 m (130-150 m)
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eccentrically located large and pale nucleus with a well-developed nucleolus
numerous free ribosomes and smaller mitochondria with arch-like oriented cristae
voluminous Golgi apparatus located near the nucleus, lately near the cell surface
few endoplasmic reticulum
absence of centrioles
 cortical granules under cell membrane, contain material of mucopolysaccharide
character
(presence of granules is the sign of maturation of an ovum)
during the sperm penetration into ovum, the content of cortical granules is released
and prevents the polyspermia = basis of the cortical reaction
 yolk = cell inclusions
chemically, yolk involves saccharides,
especially of glycogen, lipids and proteins
that mostly occur in the form of proteinaceous
lattices
amount of the yolk in human ova is low
(oligolecithal ovum)
is diffusely scattered throuhout the ooplasm
(isolecithal ovum)
greek lekithos =yolk
surface of the ovum is limited by the cell membrane, from which short microvilli project into the
zona pellucida
the zona pellucida is a clear envelope 10 to 12 m thick
it is composed of highly sulfated mucoproteins
perivitelline space= space between the cell membrane and zona pellucida
zona pellucida
Gametogenesis
process of formation and development of sex cells
the aim is to prepare sex cells to their assimilation or fusion that is a basis of fertilization
during gametogenesis, the chromosome number is reduced by half and shape of cells is
altered
Reduction of the chromosome number is achieved by
special type of cell division called meiosis; there are
two successive meiotic divisions:
the first meiotic division: homologous chromosomes
pair during prophase and separate during anaphase,
with one representative of each pair going to the
respective pole; by the end of the first meiotic division,
each new cell formed contains the haploid chromosome
number, i.e. half the original number of chromosomes
of proceeding cell (homologous chromosomes go well
together and two always form a "matched pair" whose
members are derived from each parents) - the
reduction division; disjunction of paired homologous
chromosomes is the physical basis of segregation (the
separation) of allelic genes.
the second meiotic division: follows immediately the
first division without DNA replication and without a
normal interphase, each chromosome divides in two
chromatids that are then drawn to opposite poles, the
haploid number of chromosomes is retained, and
daughter cells formed during the second division really
contain reduced chromosome number, with one
representative of every chromosome pair.
Spermatogenesis
= maturation process of male gametes; includes the series of events leading to transformation of
spermatogonia into haploid spermatids; these then develop into ripe (mature) sperms by gradual process
known as spermiogenesis (= histological differentiation of spermatids)
3 phases:
spermatocytogenesis
meiosis
spermiogenesis
the site where spermatozoa undergo their development and maturation are seminiferous
tubules of the testis
development from the spermatogonium to fully differentiated spermatozoon lasts 64 –74 days
in avarrage
spermatocytogenesis
meiosis
spermiogenesis
spermiogenesis
Oogenesis
= maturation process of female gametes
is bound to the ovary (ovarian cortex) - ovarian follicles
2 phases: oocytogenesis
meiosis
oocytogenesis - mitotic division of oogonia - begins during the fetal period
the oogonia enlarge to form primary oocytes, they enter the first meiotic division that is
stopped in the prophase, the cell nucleus is then transformed into the interphase form in which
is to stay to the beginning of reproductive life of females
meiosis
the first meiotic division is completed shortly before the ovulation - the primary
oocyte divides unequal and gives rise to large secondary oocyte and the first
polar body (polar body is nonfunctional and soon degenerates)
in time of ovulation the secondary oocyte enters the second meiotic
division that progresses only to metaphase, in which division is arrested
completion of the second meiotic division is closely connected with penetration of
the sperm into the oocyte: the division becomes again to continue and developed
daughter cells are the mature ovum and the secondary polar body
Comparison of spermatogenesis and ogenesis
 number of produced gametes – 4 spermatids vs 1 ovum (polar bodies are
nonfunctional cells that degenerate)
 course of process – continuous vs cyclic and limited only on period of sexual
maturity (400 ova)
 motility of gametes – motile with only small amount of the cytoplasm vs
immotile, the cytoplasm is abundat and contains stored material for the first week of
development
Transportation of gametes
the site of fertilisation is the uterine tube – its dilated part termed the ampula
nearly to the ovary
Oocyte transport:
to release the secondary oocyte from the graaphian follicle occurs during the
ovulation
the oocyte surrounded by some granulosa cells is expelled from the follicle
and is directed via stream of follicular fluid under contraction of fimbriae
(finger-like processes of the tube) into the lumen of the infudibulum
the oocyte then passes into the ampulla by waves of peristalsis of muscle cells in the
wall of oviduct
it is supposed that oocyte reaches the fertilization site in cca 25 min
Sperm transport:
after cohabitation, the spermatozoa deposited against the cervix
and the posterior fornix of the vagina, pass by movements of their tails through the
cervical canal into the uterus and subsequently in the respective uterine tube
the ascent is caused by contractions of smooth muscle cells in the wall of the uterus
and uterine tube
fresh spermatozoa, upon arrival in the female genital tract, are not capable to
fertilize the oocyte because
they must undergo capacitation and the acrosome reaction
Capacitation of sperm
an activation process of sperms that takes about 7 hours
during this process, a glycoprotein coat and seminal plasma proteins are removed from the plasma
membrane over the acrosome
the process does not connect with morphological aterations
spermatozoa undergo their capacitation in the uterus or uterine tube by influence of substances secreted
by these parts
Important: sperms must be capacitated also in cases of in vitro fertilization
(as capacitation media are used gamma-globulin, free serum, serum dialysate, follicular fluid, albumin,
dextran etc. - artifitial capacitation media)
The acrosome reaction
it follows the capacitation
involves a series of events that are induced by
penetration of spermatozoa through the corona
radiata
in comparison with capacitation, the process is accompanied by structural alterations - by
multiple point fusions of plasma membrane and the outer acrosomal membrane
the fused membranes then rupture to produce multiple perforations through them enzymes
contained within the acrosome escape (hyaluronidase, trypsin-like substance, acrosin)
Fertilization
is a process of fusion of male and female gametes
in average, it needs several hours ( 24 hours)
fertilization site - the ampulla of the uterine tube - is the widest segment of the tube
germ cell viability –
spermatozoa can stay alive in the
female reproductive tract for 24
hours
(there is suggestive evidence that
some sperms may fertilize an ovum
for as long as three days
after insemination)
if the ovum (the secondary oocyte)
was not fertilized, it degenerates 12
to 24 hours after ovulation
phases of fertilization:
penetration of corona radiata
penetration of zona pellucida
fusion of oocyte and sperm cell membranes
constitution of the male pronucleus
fusion of the pronuclei
1. Penetration of corona radiata
the corona radiata is envelope from follicular cells that encloses the ovulated oocyte
the main goal of this phase is dispersal of corona radiata cells by enzyme hyaluronidase
released from the acrosomal caps of spermatozoa
2. Penetration of zona pellucida
is facilitated by the action of enzymes released from the acrosome
primary role plays acrosin, enzyme causes lysis of the zone (inhibition of acrosin prevents
passage of sperms through the zona pellucida)
once the first sperm passes through the zona pellucida, so-called a zona reaction starts,
during which the zona pellucida becomes impermeable to further spermatozoa
is supposed that the zona reaction is mediated by cortical granules of the secondary oocyte
3. Fusion of oocyte-sperm cell membranes
this phase is characterised by actual fusion of the oocyte membrane and membrane
covering the posterior region of the sperm head, the head and tail of the sperm enter the
cytoplasm of the oocyte
after fusion of membranes, the secondary oocyte can complete the second meiotic division to
give rise to the mature ovum with haploid number of chromosomes and the second polar
body
chromosomes in the egg nucleus decondense to form the female pronucleus
4. Constitution of the male pronucleus
the penetrated sperm moves in close vicinity to the female pronucleus
its nucleus becomes rapidly swollen and forms the male pronucleus
(the tail of the sperm degenerates)
5. Fusion of the pronuclei
the male and female pronuclei approach each
other in the centre of the ovum and come into
contact
they lose then their nuclear membranes and
maternal and paternal chromosomes intermingle
(mix together) and they organize in an
equatorial plane
the first mitotic division of the zygote
starts /cleavage of the zygote/
Results of fertilization:
restoration of diploid number of
chromosomes (half from the mother and
half from the father)
determination of the sex of the new
individual
(XX -female, XY-male)
initiation of cleavage
(not fertilized oocyte degenerates in 12-24
hours after ovulation)
Cleavage of the zygote
the phase of development characterized by mitotic divisions of the zygote resulting in
formation of the blastocyst
cells are called blastomeres and become smaller with each division
the cleavage takes place partly in the uterine tube (during the first three days),
partly in the uterus (from day 4 to 6)
the first division resulting in 2-cell stage needs about 24 to 30 hours, subsequent
divisions follow in shorter intervals because blastomeres become progressively
smaller
TEM:
SEM:
after the eight-cell stage (three mitotic divisions), the morula stage develops
the morula - a solid ball consisting of 12 to 16 cells that lay on tightly each other
(it shows resemblance to the fruit of mulberry tree)
the morula enters the uterine cavity where is transformed into the blastocyst
Formation of the blastocyst
shortly after the morula enters the
uterus (on day 4), fluid passes from
the uterine cavity through the zona
pellucida to form a single fluid-filled
space – blastocystic cavity (primitive
chorionic cavity or blastocoele)
Consequently, the morula cells
separate into two cell lines:
an outer cell layer, the trophoblast
(greek trophé = nutrition) - gives rise to
chorion and finally fetal part of the
placenta
a group of centrally located cells,
called as the inner cell mass or
embryoblast - gives rise to the
embryo
the blastocyst is enclosed with the
zona pellucida and lies free in the
uterus cavity
during the day 6, the zona pellucida becomes to digest by enzymes contained in the uterine
fluid and soon disappears
the denuded blastocyst then expands up to diameter of 400 m or more and is prepared to
start the implantation
Early blastocyst
(with the zona)
Late (mature) blastocyst
(denuded)
Implantation
an adaptive process, during which the blastocyst
establishes very close contact with the uterine
mucosa (endometrium) of the maternal organism
main goal is to provide nutrition of the
embryoblast because yolk material has
been completely utilized during cleavage
and blastocyst formation
the implantation begins on day 7 and ends
on day 13
the trophoblast cells play key role in this
proces, they differentiate in the
cytotrophoblast and the syncytiotrophoblast
invading the uterine mucosa
Staging of the implantation:
Attaching of the blastocyst to the
endometrial epithelium
Invasion of the trophoblast cells in the
endometrium
Reparation of implantation defect in
endometrium
Formation of uteroplacental circulation
Manifestation of decidual reaction
1. Attaching of the blastocyst to the endometrial epithelium
– it follows the zona pellucida lysis; the blastocyst attaches to the endometrium with embryonic pole (the pole,
by which the embryoblast is placed)
2. Invasion of the trophoblast cells in the endometrium
follows as a result of contact of trophoblast with the endometrium
trophoblast cells proliferate and differentiate into 2 populations:
the syncytiotrophoblast located peripherally
– invades and erodes quickly the endometrial
stroma and uterine glands
it forms around the blastocyst a large, thick and
multinucleated mass without obvious cell boundaries
the erosion of the uterine mucosa is caused
by proteolytic enzymes produced by
syncytiotrophoblast cells
the cytotrophoblast (secondary trophoblast)
that gradually replaces the original trophoblast
the cytotrophoblast cells are mitotic active and form
new cell generations - migrate into the blastocyst
cavity where give rise to the extraembryonic
mesoderm or migrate externally to complete
masses of the syncytiotrophoblast
the trophoblast cell differentiation of the entire blastocyst
needs about 3 days, i.e. on day 10 a conceptus is usually
embedded within the endometrial stroma
3. Reparation of implantation defect in endometrium
after penetration of the blastocyst, the defect in the epithelium is filled with a closing plug (operculum)
– a blood clot and cellular debris
by day 12, the site of implanted conceptus appears as a minute elevation of the endometrial surface and
is covered with regenerated epithelium
4. Formation of uteroplacental circulation
around day 9, isolated spaces (cavities) called lacunae are formed in the syncytiotrophoblast
they become filled with nutrition secretions from eroded endometrial glands and with maternal blood
from ruptured maternal capillaries – histiotroph
later, between day 11 and 13, adjacent lacunae fuse to form lacunar network in which maternal vessels
open and through which maternal blood flows
5. Manifestation of decidual reaction
the conceptus evokes reaction of the entire endometrium
consists in endometrial stromal cell changes that enlarge and accumulate glycogen and lipid droplets, in
vascular alterations (capillary network around the conceptus becomes denser), and glandular alterations
– uterine glands increase their activity
changes are referred to as the decidual reaction
and the decidual transformed endometrium to as the decidua
The decidua involves 4 distinct regions as follows:
 basal decidua - under the conceptus
 marginal decidua - at the side of the conceptus
 capsular decidua - above the conceptus
 parietal decidua - has no contact with the conceptus
Implantation sites of the blastocyst
Intrauterine sites:
normally, the blastocyst implants on the posterior wall of the midportion of the uterus body
important: nidation near the internal ostium – the developing placenta covers the internal
ostium as placenta previa
it causes severe bleeding during pregnancy (it usually occurs in the 28th week) or during the
labor
Extrauterine sites:
if blastocyst achieves the mature blastocyst stage (without zona pellucida), it starts to implant
in the site where is just
- implantation in the uterine tube (ectopic tubal pregnancy) - is represents about 90 %
ectopic pregnancies; tubal pregnancy usually results in rupture of the uterine tube and
hemorrhage during the first 8 weeks, followed by death of the embryo
- implantation in the ovary (ectopic ovarian pregnancy)
ectopic pregnancies are connected with profuse hemorrhage