GENERAL

EMBRYOLOGY

Lecture 1
 Objectives
 To help understand how normal
development occurs from conception to
birth.

 To understand the principle of

teratogenesis and the basis of birth defects

 To understand the developmental basis in

the study and practice of medicine
Introduction
 Human embryology can be defined as a continuous process that
begins when an oocyte (ovum) from a female is fertilized by a
sperm (spermatozoon) from a male.
 This is followed by continuous Cell division, cell migration,
programmed cell death, differentiation, growth and cell
rearrangement that transform the zygote, into a multi-cellular
human being.
 Most developmental changes occur during the embryonic and fetal
periods, though important changes occur during later periods of
development including infancy, childhood, adolescence, and early
adulthood

 NB >Development does not stop at birth. Important changes, in

addition to growth, occur after birth (e.g., development of teeth and
female breasts).
 Why study Embryology?

 Embryology is the study 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.
 Teratology (Gr. teratos, monster) is the division of
embryology and pathology that deals with abnormal
development (birth defects).
 The branch of teratology:- is concerned with various
genetic and/or environmental factors that disturb
normal development giving rise to birth defects
 Ctd’
 Embryology Bridges the gap between prenatal
development and obstetrics, perinatal medicine,
pediatrics, and clinical anatomy.
 It develops knowledge concerning the beginnings of
human life and the changes occurring during prenatal
development.
 It helps in understanding the causes of variations in
human structure.
 It also helps in understanding gross anatomy and
explaining how normal and abnormal relations
develop.
 DEVELOPMENTAL PERIODS
 Human development is usually divided into two
broad periods:
1. Prenatal development- (before birth):
- most visible advances occur during the third
to eighth weeks a.k.a embryonic period.
- after 8th weeks the fetal period, is
characterized with differentiation and growth of
tissues and organs occur. The rate of body
growth increases during this period
2. Postnatal development- (after birth): further
differentiation of organs and specializations of
body tissues
 Embryonic terminologies
 Oocyte :- The female germ or sex cells produced in the ovaries. When mature,
the oocytes are called secondary oocytes or mature oocytes.
 Sperm:-. The sperm, or spermatozoon, refers to the male germ cell produced in
the testes (testicles). Numerous sperms (spermatozoa) are expelled from the male
urethra during ejaculation.
 Zygote:- The cell that results from the union of an oocyte and a sperm during
fertilization and marks the beginning of a new human being.
 Gestational Age.:- it is the period from fertilization to birth: it is usually divided
into three trimesters (I,II,II)
NB> It is difficult to determine exactly when fertilization (conception) occurs
because the process cannot be observed in vivo (within the living body, it is
therefore calculated from the presumed first day of the last normal menstrual
period. >> which is approximately 2 weeks longer than the fertilization age
because the oocyte is not fertilized until approximately 2 weeks after the
preceding menstruation
 Cleavage:- This is the series of mitotic cell divisions of the zygote that result in
the formation of early embryonic cells, blastomeres. The size of the cleaving
zygote remains unchanged because at each succeeding cleavage division, the
blastomeres become smaller.
 Morula :- This solid mass of 12 to approximately 32 blastomeres formed
during cleavage of a zygote that tightly align themselves against each other
to form a compact ball of cells through a process called compaction and
mediated by cell surface adhesion glycoproteins. (NB> morula stage occurs
3 to 4 days after fertilization as it enters the uterus).
 Blastocyst:- This is a fluid-filled cavity, the blastocystic cavity, that
develops inside the morula 2 to 3 days after entering the uterus from the
uterine tube (fallopian tube).
 Embryoblast or inner cell mass :- this is the centrally located cells of
the blastocyst and they form the embryonic part of the embryo.
 Implantation:- The process during which the blastocyst attaches to the
endometrium, the mucous membrane or lining of uterus, and subsequently
embeds in it.
 The preimplantation period:- this is the time between fertilization and
the beginning of implantation, a period of approximately 6 days.
 Gastrula (Gr. gaster, stomach). It is the transformation of a blastocyst
inner cell mass (embryoblast) into a three-layered or trilaminar embryonic
disc forms (third week). The three germ layers of the gastrula (ectoderm,
mesoderm, and endoderm).
 Embryonic period:- it is the period that extends to the end of the
eighth week (56 days), and marks the beginnings of all major organs
 NB> The size of embryos is given as crown-rump length, which is measured
from the vertex of the cranium (crown of head) to the rump (buttocks).
Stages of Prenatal Development. We shall study it in the following
stages of development:
– Stage 1:- embryonic stage that will be from fertilization and embryonic development up to
day 56.
– Stage 2:- the fetal stage: The fetal period begins on day 57 and ends when the fetus is
completely outside the mother.
 Conceptus :- The embryo and its associated membranes. I.e the embryo
as well as the embryonic part of the placenta and its associated
membranes: amnion, chorionic (gestational) sac, and umbilical vesicle or
yolk sac. The conceptus includes all structures that develop from the zygote,
both embryonic and extra-embryonic.
 Primordium (L. primus, first + ordior, to begin) - The beginning or first
discernible indication of an organ or structure. E.g the primordium of the
upper limb appears as a bud on day 26 .
 Fetus (unborn offspring) - After the embryonic period (8 weeks) and
until birth, the developing human is called a fetus.
Early Human Development

 Zygote
 Blastomeres
 Morula
 Blastocyst
 Embryo
 Fetus
 Conceptus
 Abortion (L. aboriri, to miscarry). A premature stoppage of
development and expulsion of a conceptus from the uterus or expulsion of
an embryo or fetus before it is viable of living outside the uterus.
 An abortus is the products of an abortion (i.e., the embryo/fetus and its
membranes). The different types of abortion includes:-
1. Threatened abortion (bleeding with the possibility of abortion):- is a
complication in approximately 25% of clinically apparent pregnancies. Despite every
effort to prevent an abortion, approximately half of these abort.
2. A spontaneous abortion:- is one that occurs naturally and is most common during
the third week after fertilization. Approximately 15% of recognized pregnancies end
in spontaneous abortion, usually during the first 12 weeks.
3. A habitual abortion:- is the spontaneous expulsion of a dead or nonviable embryo
or fetus in three or more consecutive pregnancies.
4. An induced abortion:- is a birth that is medically induced intentionally by drugs or
mechanical before 20 weeks (i.e., before the fetus is viable).
5. A complete abortion is one in which all the products of conception are expelled
from the uterus.
6. A missed abortion :- is the retention of an embryo or fetus in the uterus after
death
7. A miscarriage:- is the spontaneous abortion of a fetus and its membranes before
the middle of the second trimester (approximately 135 days).
Stages and Time Frames

 Ovum
 Zygote

 Morula

 Blastocyst

 Embryo

 Fetus

(Oh, Zee my baby eats

fast)
 Gametogenesis
Dfn: Conversion of Germ Cells Into Male and
Female Gametes.

Primordial Germ Cells (primitive sex cells): the

male(sperms) and female gametes(oocyte).
Both unite during fertilization to give rise to a
zygote.
During gametogenesis, the chromosome number
is reduced by half and the shape of the cells is
altered. This process prepares these sex cells
for fertilization.
 Primodial germ cells for gametogenesis
Primordial germ cells appear in the wall of the yolk sac in the fourth
week and migrate to the indifferent gonad where they arrive
at the end of the fifth week.

In preparation for fertilization, both male and female germ cells undergo
gametogenesis, which includes meiosis and cytodifferentiation.

Gametogenesis: Conversion of Germ Cells Into Male and Female Gametes

During meiosis I, homologous chromosomes pair and exchange
genetic material;
during meiosis II, cells fail to replicate DNA, and each cell is thus provided
with a haploid number of chromosomes and half the amount of DNA of a
normal somatic cell

NB>> Hence, mature male and female gametes have, respectively, 22 plus X
or 22 plus Y chromosomes.
 The Chromosome Theory of Inheritance
 Traits of an individual are determined by specific
genes on chromosomes inherited from the father and
the mother
NB> Humans have approximately 35,000 genes on
46 chromosomes.
 Somatic cells have 23 homologous pairs of
chromosomes that form the diploid number of 46
 sex cells have 22 pairs of matching chromosomes-
autosomes, and one pair of sex chromosomes that
can either be XX or XY
 .
Mitosis : The process whereby one cell
divides, giving rise to two daughter cells that
are genetically identical to the parent cell.
-it has four phases: prophase, metaphase
anaphase and telophase,
 Meiosis: is the cell division that takes place in
the germ cells to generate male and female
gametes, sperm and egg cells-oocyte
- It has two cell divisions, meiosis I and meiosis
II, to reduce the number of chromosomes to
the haploid number of 23.
 Review on Types of cell division
 Prokaryotes
– Binary fission

 Eukaryotes

– Mitosis:
 Growth, development & repair.

 Asexual reproduction (yields genetically identical cells).

 Occurs in somatic (body) cells.

– Meiosis:
 Sexual reproduction (yields genetically different cells with half
the number of chromosomes).
 Occurs in specific reproductive cells.

 Yields gametes (e.g., eggs & sperm) or spores.

 Mitosis is conventionally divided into five phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
 Cytokinesis is well underway by late telophase
Key Differences between mitosis & meiosis
 In contrast to mitosis, homologous chromosomes in
meiosis align themselves in pairs, a process called
synapsis.
 In meiosis there is crossover: involves
interchange of chromatid segments between paired
homologous chromosomes-exchange of genetic
material-for genetic variability
> This pairing is exact and point for point except for
the XY combination. Homologous pairs then separate
into two daughter cells. Shortly thereafter meiosis II
separates sister chromatids.
>Each gamete then contains 23 chromosomes.
 Important features of meiosis
a) Genetic variability is enhanced through:
 Crossover, which redistributes genetic material,
and through random distribution of homologous
chromosomes to the daughter cells

(b) Each germ cell Contains a haploid number of

chromosomes, so that at fertilization it restores
the diploid number of chromosomes
Primordial Germ Cells and Teratomas

 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 differentiate into any
of the three germ layers or their derivatives.
 Chomosomal abnormalitis and Birth defects
 Birth defects/congenital anomalies may arise
through abnormalities in chromosome
number or structure and from
single/multiple gene mutations.

 Approximately 7% of major birth defects are a

result of chromosome abnormalities, and 8%,
are a result of gene mutations.

 The incidence of abnormalities of chromosome

number increases with age of the mother,
particularly with mothers aged 35 years and
older.
 Numerical chromosomal abnormalities

 Euploid: - Euploid refers to any exact multiple of n,

e.g., diploid or triploid.(i.e triploidy, monoploidy,
tetraploiday etc)
 Non-disjunction: where both members of the paired
chromosome move into one cell resulting into one cell
receiving 24 chromosomes,and the other receives 22
instead of the normal 23.
 Mitotic nondisjunction/mosaicism: non
separation of chromosomes in an embryonic cell
during the earliest cell divisions. Such conditions give
rise to some cells having abnormal and other normal
number of cells (mosaicism).
 Structural abnormalities of chromosomes
 Structural abnormalities due to deletion of chromosomes include

1. large deletions (cri-du-chat syndrome) and

2. Microdeletions - Microdeletions involve contiguous genes that may result in
defects such as :-
(a) Angelman syndrome (maternal deletion, chromosome 15q11–
15q13 or
(b) Prader-Willi syndrome (paternal deletion, 15q11–15q13).

Because these syndromes depend

 on whether the affected genetic material is inherited from the mother or
the father, they also are an example of imprinting.
 Gene mutations may be dominant (only one gene of an allelic pair has
to be affected to produce an alteration)
 or recessive (both allelic gene pairs must be mutated). Mutations
responsible for many birth defects affect genes involved in normal
embryological development.
 Trisomy18: show the following features: mental
retardation, congenital heart defects, low-set ears,and
flexion of fingers and hands ,renal
anomalies,syndactyly, and malformations of the
skeletal system etc

 Klinefelter syndrome: The cells have 47

chromosomes with a sex chromosomal complement of
the XXY type, and a sex-chromatin
-found only in males and usually detected at puberty,
are sterile, testicular atrophy, hyalinization of the
seminiferous tubules, and usually gynecomastia.
 Prader-Willi syndrome: is produced by inheriting
a defective paternal chromosome. affected
individuals are characterized by:- hypotonia, obesity,
mental retardation, hypogonadism, and
cryptorchidism

 Miller-Dieker syndrome : contiguous gene

syndromes that may be inherited from either parent,
including (lissencephaly, developmental
delay,seizures,and cardiac and facial abnormalities

 schizophrenia-like disorder; results from

deletion: features :-palatal defects, conotruncal
heart defects, speech delay, learning disorders, and
resulting from a deletion
 DiagnosticTechniques for
IdentifyingGenetic Abnormalities
1. Cytogenetic analysis:used to assess chromosome number
and integrity. The technique requires dividing cells, which usually means
establishing cell cultures that are arrested in metaphase by chemical
treatment.( Gemsa stain is used)

2. high resolution metaphase banding

techniques:- it is a new highly specialized method used in
making diagnosis of small deletions in a chromosome.

3. fluorescence in situ hybridization:New molecular

techniques that uses specific DNA probes to identify ploidy for a few
selected chromosomes or genetic loci using cells on a slide.
 Morphological Changes During Maturation
of the Gametes
 Oogenesis (in female):-:includes all of the
events by which primary oocyte are
transformed into an ovum.
NB> Maturation of ovum Begins at birth

 Spermatogenesis(in males):- includes all of

the events by which spermatogonia are
transformed into spermatozoa.
NB>Maturation of Sperm Begins at Puberty
 oogenesis
 Primordial germ cells from the walls of the yolk sac
migrate through amoeboid movement to the female
gonads(ovary)
 They become surrounded with flat cells called follicular
cells derived from the surface epithelium of ovary:-
 These cells continue to divide through mitotic division
and becomes arrested at prophase of meiosis one:-
now called [primary oocyte)-7million
 Most of these cell in the middle of the ovary die
off/become atretic remaining those at the periphery.
 FEMALE ovary

GERMINAL EPITHELIUM

TUNICA ALBUGINEA
- thin connective tissue
capsule underlying germinal
epithelium

CORTEX
- surrounds the medulla and
contains maturing follicles

MEDULLA
- central connective tissue
containing vascular supply
and nervous innervation
 FEMALE REPRODUCTIVE SYSTEM
 OVIDUCT (UTERINE TUBES)

INFUNDIBULUM, AMPULLA, ISTHMUS, UTERINE

 UTERUS

FUNDUS, BODY (CORPUS), CERVIX

 FEMALE REPRODUCTIVE
SYSTEM
 OVARY

3 to 5 million OOGONIA differentiate into

PRIMARY OOCYTES during early
development
OOCYTES becomes surrounded by
squamous (follicular) cells to become
PRIMORDIAL FOLLICLES
most PRIMORDIAL FOLLICLES undergo
atresia leaving 400,000 at birth

NB> oocytes at birth

arrested at Meiosis I
(prophase) = called
diplotine stage
 FEMALE REPRODUCTIVE
SYSTEM
 OVARIAN FOLLICLES

(1) PRIMORDIAL FOLLICLES

(2) GROWING FOLLICLES
(a) early primary follicle
- follicular cells still unilaminar but now are cuboidal in
appearance
- oocyte begins to enlarge
(b) late primary follicle
- multilaminar follicular layer; cells now termed granulosa cells
- zona pellucida appears; gel-like substance rich in GAGs
- surrounding stromal cells differentiate
into theca interna and theca externa
(b) secondary (antral) follicle
- cavities appear between granulosa cells forming an antrum
- follicle continues to grow
- formation of cumulus oophorus and corona radiata

(3) MATURE (GRAAFIAN) FOLLICLES

 FEMALE REPRODUCTIVE
SYSTEM
 OVARY

MATURE (GRAAFIAN)
FOLLICLE

zona pellucida
cumulus oophorus
corona radiata
theca interna and externa
theca interna cells begin to
produce androgens that are
converted to estrogens
 Maturation of the female gametes

 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, primordial germ cells form oogonia. After repeated mitotic
divisions, some of these arrest in prophase of meiosis I to form primary
oocytes.
 By the seventh month, nearly all oogonia have become atretic, and only
primary oocytes remain surrounded by a layer of follicular cells derived
from the surface epithelium of the ovary-they form the primordial follicle.
 At puberty, everyday 15 to 20 follicles begin to grow, and as they mature,
they pass through three stages: 1) primary or preantral; 2) secondary
or antral (vesicular, Graafian); and 3) preovulatory.
 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 a
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.
.
 SPERMATOGENESIS
 Dfn: process by which spermatogonia is
transformed into spermatozoa
>>Begins at puberty:
 At birth, germ cells in the male can be
recognized in the sex cords of the testis as
large, pale cells surrounded by supporting cells
 The Supporting cells are derived from the
surface epithelium of the testis in the same
manner as follicular cells of the ovary-
becomes:-stentacular cells, or Sertoli cells.
Spermatogenesis Ctd’
 Shortly before puberty, the sex cords
acquire a lumen and become the
seminiferous tubules.

 At about the same time, primordial

germ cells give rise to spermatogonial
stem cells
Male repoductive system
The testis
 Spermatogenesis and spermiogenesis
 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 (a) formation of
the acrosome, (b) condensation of the nucleus, (c)
formation of neck, middle piece, and tail, and (d)
shedding of most of the cytoplasm.
 The time required for a spermatogonium to become a
mature spermatozoon is approximately 64 days.
Problems to Solve

1. What is the most common cause of

abnormal chromosome number?
2.Give an example of a clinical syndrome
involving abnormal numbers of
chromosomes.
2. In addition to numerical abnormalities,
what types of chromosomal
alterations occur?
3. What is mosaicism, and how does it occur?
 First Week of Development:
Ovulation to Implantation
 At puberty, the female begins to undergo regular
monthly cycles. These sexual cycles are controlled
by the hypothalamus through release of
Gonadotropin-releasing hormone(GnRH)
 The GnRH acts on cells of the anterior pituitary
gland, which in turn secrete gonadotropins that
include- the follicle-stimulating hormone (FSH)
and luteinizing hormone (LH),
 These two hormone stimulate and control cyclic
changes in the ovary.
 Ctd’
 At the beginning of each ovarian cycle, 15 to
20 primary (preantral) stage follicles are
stimulated to grow under the influence of FSH.

 Under normal conditions, only one of these

follicles reaches full maturity, and only one
oocyte is discharged; the others degenerate
and become atretic
 Ctd’
 When a follicle becomes atretic, the oocyte and surrounding
follicular cells degenerate and are replaced by connective
tissue, forming a corpus atreticum.
 FSH also stimulates maturation of follicular (granulosa) cells
surrounding the oocyte.
 The granulosa and thecal cells produce estrogens that;-

(a) cause the uterine endometrium to enter the follicular or

proliferative phase;
(b) cause thinning of the cervical mucus to allow passage of
sperm; and
(c) stimulate the pituitary gland to secrete LH. At mid-cycle,
there is an LH surge;
- that 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); and
- causes follicular rupture and ovulation.
 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 luteal
cells, which form the corpus luteum and
secrete the hormone progesterone
 OOCYTE TRANSPORT
 Shortly before ovulation, fimbriae of the oviduct
begin to sweep over the surface of the ovary, and
the tube itself begins to contract rhythmically.

 It is thought that the oocyte surrounded by some

granulosa cells is carried into the tube by these
sweeping movements of the fimbriae and by
motion of cilia on the epithelial lining the uterine
tubes.

 In humans, the fertilized oocyte reaches the

uterine lumen in approximately 3 to 4 days.
 CORPUS ALBICANS

 If fertilization does not occur, the corpus

luteum reaches maximum development
approximately 9 days then shrinks because of
degeneration of lutean cells and forms a mass
of fibrotic scar tissue, the corpus albicans.

 Simultaneously, progesterone production

decreases, precipitating menstrual bleeding
 Ctd’
 If the oocyte is fertilized, degeneration
of the corpus luteum is prevented by human
chorionic gonadotropin (hCG), an 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).
 It continues to secrete progesterone until the end of
the fourth month; thereafter, they regress slowly as
secretion of progesterone is by the trophoblastic
component of the placenta for maintenance of
pregnancy.
Fertilization

 Defn: The
T process by which male and
female gametes fuse,
 It occurs in the ampullary region of
the uterine tube
 Fertilization ctd’
 Spermatozoa may remain viable in the female reproductive
tract for several days.
 Only 1% of sperm deposited in the vagina enter the cervix,
where they may survive for many hours.
 Movement of sperm from the cervix to the oviduct is
accomplished primarily by their own propulsion, although they
may be assisted by movements of fluids created by uterine
cilia.
 The trip from cervix to oviduct requires a minimum of 2 to 7
hours, and after reaching the isthmus, sperm become less
motile and cease their migration.
 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.
Fertilization ctd’
 Spermatozoa are not able to fertilize the oocyte
immediately upon arrival in the tract but must
undergo
1. capacitation and
2. acrosomal reaction to acquire this capability.

-Capacitation is a period of conditioning in the

female reproductive system and lasts approximately 7
Hours – entails removal of glycoprotein coat
and seminal plasma proteins from the plasma
membrane that overlies the acrosomal region of the
spermatozoa.
 Fertilization ctd’

 The acrosomal reaction, -occurs after

binding to the zona pellucida, and is induced
by zona proteins.
-This reaction culminates in the release of
enzymes needed to penetrate the zona
pellucida, including acrosin and trypsin-like
substances.
 The phases of fertilization
 phase 1: penetration of the corona radiata;
 phase 2: penetration of the zona pellucida;
 phase 3: fusion of the oocyte and sperm
cell membranes.
The response of the egg (oocyte) to the
spermatozoa
As soon as the spermatozoon has entered the oocyte, the egg responds in three ways:
1. Cortical and zona reactions. Includes (a) the oocyte membrane
becomes impenetrable to other spermatozoa, and (b) 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).
2. Resumption of the second meiotic division. The oocyte finishes its second
meiotic division immediately after entry of the spermatozoon. One
of the daughter cells, which receives hardly any cytoplasm, is known as
the second polar body; the other daughter cell is the definitive oocyte.
Its chromosomes (22+X) arrange themselves in a vesicular nucleus
known as the female pronucleus.
3. Metabolic activation of the egg. The activating factor is probably carried
by the spermatozoon. Postfusion activation may be considered to encompass the
initial cellular and molecular events associated with early embryogenesis.

 The spermatozoon, meanwhile, moves forward until it lies close to the female
pronucleus.
 Results of fertilization

The main results of fertilization are as follows:

1.Restoration of the diploid number of
chromosomes, half from the father and half from the
mother. Hence, the zygote contains a new
combination of chromosomes different from both
parents.
2.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.
3. Initiation of cleavage. Without fertilization, the
oocyte usually degenerates 24 hours after ovulation.
FERTILIZATION

 Begins with 46 pair of chromosomes, splits off to

23 then combine for a unique new 46 pair.
Fertilization of the Ovum
and Cleavage of the Zygote
 Moore, fig3-5
 Contraceptive Methods
 Barrier techniques of contraception include:-
1. male condom, made of latex and often containing
chemical spermicides, which fits over the penis;
2. the female condom, made of polyurethane, which
lines the vagina.
3. Other barriers placed in the vagina include the
diaphragm, the cervical cap, and the contraceptive
sponge.
 The contraceptive pill is a combination of estrogen
and the progesterone analogue progestin, which
together inhibit ovulation but permit menstruation.
Contraceptives ctd’
 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,
respectively.

 A male “pill” has been developed and tested in clinical trials. It contains a
synthetic androgen that prevents both LH and FSH secretion and either stops
sperm production (70–90% 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.

 The drug RU-486 (mifepristone) causes abortion if it is administered

within 8 weeks of the previous menses. It initiates menstruation, possibly
through its action as an antiprogesterone agent.

 Vasectomy and tubal ligation are effective means of contraception, and

both procedures are reversible, although not in every case.
Infertility and causes of
infertility
Infertility is a problem for 15% to 30% of couples.
A) Male infertility may be a result of:- insufficient
numbers of sperm and/or poor motility. Normally,
the ejaculate has a volume of 3 to 4 ml, with
approximately 100 million sperm per ml. Males with
20 million sperm per ml or 50 million sperm per
total ejaculate are usually fertile.
B) Infertility in a woman may be due to a number of
causes, including:- occluded oviducts (most
commonly caused by pelvic inflammatory
disease), hostile cervical mucus, immunity to
spermatozoa, absence of ovulation, and many
others.
 CLEAVAGE
 Once the zygote has reached the two-cell stage, it
undergoes a series of mitotic divisions, increasing the
numbers of cells.
 These cells, which become smaller with each cleavage
are known as blastomeres
 Until the eight-cell stage, they form a loosely arranged
clump
 After the third cleavage, blastomeres maximize their
contact with each other, forming a compact ball via a
Process called compaction, segregating inner
cells
 Approximately 3 days after fertilization, cells of the
compacted embryo divide again to form a 16-cell
morula (mulberry).

 Inner cells of the morula constitute the inner cell

mass, and surrounding cells compose the outer
cell mass.

 The inner cell mass gives rise to tissues of the

embryo proper, and the outer cell mass forms the
trophoblast, which later contributes to the
placenta
Cleavage & compaction
Compaction SEM
 .
cleavage
Blastocyst Formation
 By the time the morula enters the uterine cavity,
fluid begins to penetrate into the intercellular spaces
of the inner cell mass.
 Gradually the intercellular spaces become confluent,
and finally a single cavity, the blastocele - the
embryo is now called blastocyst
 Cells of the inner cell mass, now called the
embryoblast, are at one pole, and those of the
outer cell mass, or trophoblast, flatten and form
the epithelial wall of the blastocyst.
 The zona pellucida has disappeared, allowing
implantation to begin.
 The embryoblast pole begin to penetrate
the uterine mucosa about the sixth day
 This Attachment and invasion of the trophoblast
involve integrins, expressed by the trophoblast, and
the extracellular matrix molecules laminin and
fibronectin.
 Integrin are receptors for laminin promote
attachment, while those for fibronectin stimulate
migration
NB > These molecules interact along signal
transduction pathways to regulate trophoblast
differentiation so that implantation is a mutual
trophoblastic and endometrial action
Implantation
– Moore, fig 3-4
Implantation of the developing
Embryo
The zygote is a foreign body (Not Self)

Immunosuppressive cytokines protect the

conceptus as well as the production of a special
histo-compatibility protein that blocks the
recognition of the embryo by the immune system.

Mothers with autoimmune disorders such as Lupus

erythematosus have antibodies generated by the
disease that attack the embryo and reject it.

The immuno-suppressed female reproductive tract

is acidic to protect it from infection
 Ectopic Pregnancies
Rectouterine
Cavity

Placenta
Previa
Most
Common
(95%)
 Implantation cont’d
The developing embryo must force its way through the
Uterine Epithelium.
The Trophoblast cells at the embryonic pole begin to proliferate.

Trophoblast
 Changes in the uterus during
implantation
under normal circumstances the uterus has got
three layers:
(a) endometrium or mucosa lining the inside
wall
(b) myometrium, a thick layer of smooth
muscle
(c) perimetrium, the peritoneal covering
lining the outside wall
 During this menstrual cycle, the uterine
endometrium passes through three stages:

1. The follicular or proliferative phase,

2. The secretory or progestational phase,
and
3. The menstrual phase
 FEMALE REPRODUCTIVE
SYSTEM
 HORMONAL REGULATION OF UTERINE CYCLE
(1) PROLIFERATIVE concurrent with follicular maturation and influenced by
PHASE estrogens
(2) SECRETORY PHASE concurrent with luteal phase and influenced by progesterone
(3) MENSTRUAL PHASE commences as hormone production by corpus luteum
declines
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

PROLIFERATIVE PHASE

cells in basal layer begin to

proliferate to regenerate
functional layer
spiral arteries begin to
lengthen and revascularize
developing layer
functional layer becomes
thicker than basal layer during
late proliferative phase

developing uterine glands are

tubular in arrangement
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

PROLIFERATIVE PHASE

tubular uterine glands

simple columnar lining
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

PROLIFERATIVE PHASE UTERUS

H&E
PROLIFERATIVE PHASE
tubular uterine glands
simple columnar lining

UTERINE
GLANDS
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

SECRETORY PHASE

functional layer thickens

glands become coiled and
accumulate large quantities
of secretory product
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

UTERUS
SECRETORY PHASE H&E
SECRETORY PHASE

functional layer
thickens

glands coiled
COILED
UTERINE
GLANDS
 FEMALE REPRODUCTIVE
SYSTEM
 UTERUS

SECRETORY PHASE

functional layer thickens

glands become coiled and
accumulate large quantities
of secretory product
 Uterus At the time of
implantation
 The mucosa of the uterus is in the secretory
phase where the uterine glands and arteries
become coiled and the tissue becomes succulent.
 The endometrium differentiates into three layers
1: a superficial compact layer,
2: an intermediate spongy layer,
3: a thin basal layer
leavage, Implantation, and Placenta formation
Second Week of Development:

Bilaminar Germ Disc

Second week of Development is the Week to twos
 Trophoblast differentiates into 2 layers:
– The syncytiotrophoblast and
– The cytotrophoblast.

 The embryoblast (Inner Cell Mass) splits into 2 layers:

– The epiblast (forms the embryo) and
– The hypoblast.

 The extraembryonic mesoderm splits into 2 layers:

– The extraembryonic somatopleure and
– The extraembryonic splanchninopleuric mesoderm

 Two cavities form:

– The amniotic cavity and
– The yolk sac.
 The Trophoblast forms two Layers:
The Cells of the Syncyiotrophoblast fuse (form a syncytium).
The Cells of the Cytotrophblast proliferate and secrete hydrolytic
enzymes that dissolve the extracellular matrix of the Uterine
epithelium.

Uterine
epithelium

ICM Splits
to form
Epiblast
and
Hypoblast

Bilaminar
Germ Disc
 Day 8
The expanding Cytotrophoblast pulls the embryo into the Endometrium
of the uterus.

Epiblast
Proliferates and
forms the
Aminiotic Cavity

Primary ectoderm

Primary endodem
 Events of the 8th day of development
1. The blastocyst is partially embedded in the endometrial stroma
2. The trophoblast differentiates into two layers:
(a) an inner layer of mononucleated cells, the cytotrophoblast,
(b) an outer multinucleated zone without distinct cell boundaries,
the syncytiotrophoblast
3. The inner cell mass or embryoblast also differentiate into two
layers:
(a) a layer of small cuboidal cells adjacent to the blastocyst cavity,
known as the hypoblast layer, and
(b) a layer of high columnar cells adjacent to the amniotic
cavity, the epiblast layer
4. The amniotic cavity and primary yolk sac forms while the
adjacent cells close to the cytotrophoblast becomes the
amnioblasts
5.The endometrial stroma adjacent to the
implantation site is edematous and highly
vascular.
6. The large, tortuous glands secrete abundant
glycogen and mucus.
Events of 9th day of embryonic development

1. The blastocyst is fully embedded in the endometrium,

and the penetration defect in the surface epithelium
is closed by a fibrin coagulum plug.
2. Vacuoles appear in the syncytiotrophoblast and fuse
to form large lacunae, thus it is known as the lacunar
stage
3. Flattened cells originating from the hypoblast form a
thin membrane, the exocoelomic (Heuser’s)
membrane, that lines the inner surface of the
cytotrophoblast - enclosing the primary yolk sac
(exocoelomic cavity)
 Day 9 of embryonic development
•Embryo fully embedded into endometrium leaving the
Coagulation plug
•Syncyiotrophoblast expands and spaces form.
•Hypoblast expands making the primary yolk sac
•Amnioblasts arise from the epiblast. Will form the amnion

Maternal
Capillaries
invade the
lacuna
 Days 10 and 11
Formation of the primary yolk sac
Epiblast produces extraembryonic mesoderm

Acellular

Extraembryon
ic mesoderm
forms two
layers
 Events of day 10 &11
1. The blastocyst now produces a slight protrusion into the lumen
of the uterus
2. The trophoblast is characterized by lacunar spaces in the
syncytium that form an intercommunicating network
3. Syncytiotrophoblast penetrate deeper into the
stroma and erode the endothelial lining of the maternal
capillaries that become congested and dilated, forming
sinusoids
4. As more and more maternal blood begins to flow through the
trophoblastic sinusoidal system, the utero-placental
circulation is established.
5. A new population of cells appears between the inner
surface of the cytotrophoblast and the outer surface of the
exocoelomic cavity and amnion- extraembryonic
mesoderm
6. Soon, large cavities develop in the extraembryonic mesoderm,
and when these become confluent, they form a new space
known as the extraembryonic coelom, or chorionic cavity
7. This space surrounds the primitive yolk sac and amniotic cavity
except where the germ disc is connected to the trophoblast by
the connecting stalk.
8. The extraembryonic mesoderm lining the amnion is called the
extraembryonic somatopleuric mesoderm; and the one
the lining the yolk sac is known as the extraembryonic
splanchnopleuric mesoderm
NB>Growth of the bilaminar disc is relatively slow compared with
that of the trophoblast; consequently, the disc remains very
small (0.1–0.2 mm)
9. Cells of the endometrium undergoes decidua reaction. I.e
a)become polyhedral and loaded with glycogen and lipids;
b)intercellular spaces are filled with extravasate, and
Expansion of the extraembryonic
mesoderm and the hollowing out of the
chorionic cavity
 Day 12 and 13
Second wave of hypoblast proliferation and produces a layer inside the
extraembryonic mesoderm forming the definative yolk sac

Primary
yolk sac
reminants
Events of day 12 &13
1. The surface defect in the endometrium has healed but
Occasionally bleeding occurs at the implantation site as a
result of increased blood flow into the lacunar spaces.
NB> this can be confused with normal menses confusing the expected Day
of delivery
2. Cells of the cytotrophoblast proliferate locally and penetrate
into the syncytiotrophoblast, forming cellular columns
surrounded by syncytium and are called primary villi
3. The hypoblast produces additional cells that migrate along the
inside of the exocoelomic membrane , forming the the
secondary yolk sac or definitive yolk sac.
4. The extraembryonic coelom expands and forms a large cavity,
the chorionic cavity.
5. The extraembryonic mesoderm lining the inside of the
cytotrophoblast is then known as the chorionic plate.
Expansion of the extraembryonic
mesoderm and the hollowing out of the
chorionic cavity
 Day 14
Definitive yolk sac loses contact with primary yolk sac
The amnion is dorsal and the yolk sac is ventral

Secondary
Stem villus

Chorionoic
cavity
 With development of blood vessels, the stalk
becomes the umbilical cord.
 The syncytiotrophoblast is responsible for
production of hormone human chorionic
gonadotropin (hCG).
 By the end of the second week, quantities of
this hormone are sufficient to be detected by
radio-immunoassays, which serve as the
basis for pregnancy testing.
Abnormal implantation sites
Development of the Utero-plactental Circulation

Maternal capillaries enlarge and grow into

the intervillous spaces surrounding the
embryo.

The Stem Villi develop into the fetal

vasculature

Undergoes changes as the placenta grows

 Formation of the Uteroplacental Circulation

Primary Stem Villus

Extensions of the
syncytiotrophoblast protrude
away from the embryo

Secondary Stem Villus

Expansion of the extraembryonic
Mesoderm

Teritary Stem Villus

Endothelial cells from the
yolk sac form tubes that
become the fetal vasculature
 A little bigger picture
ternal vasculature develops around the embryo

Maternal
sinusoid
The developing placenta
Early uteroplacental circulation
Initially the Maternal blood supply is separated
from the embryonic blood supply by four layers.
This is remodeled later, thins such that only two
layers separate maternal from fetal.

Early placental Membrane Late placental Membrane

1) Syncytiotrophoblast
1) Syncytiotropholast
2) Endothelium of the fetal vessel
2) Cytotrophoblast

3) Connective tissue of villus core

4) Endothelium of the fetal vessel

Mature utero-placental circulation
Third Week of Development

Trilaminar Germ Disc

 Gastrulation

“Its not birth, marriage, or death, but

gastrulation, which is truly the most
important time in your life”
Lewis Wolpert (1996)

Embryonic disc is drastically rearranged.

Cells move to positions and interact with
other cells and substances that will
ultimately determine the structures they
will become.
 Gastrulation is the most characteristic event of the 3 rd
week.

 It involves formation of Embryonic ectoderm,

Mesoderm and Endoderm

 Gastrulation begins with formation of the primitive streak on

the surface of the epiblast.

 In a 15- to 16-day embryo, it is clearly visible as a narrow

groove with slightly bulging regions on either side. The cephalic
end of the streak consists of a slightly elevated area the
primitive node, surrounding a small pit the primitive pit
Formation of the streak
 Cells of the epiblast proliferate and migrate
towards the primitive streak and Upon arrival in
the region they become flask-shaped, detach
from the epiblast and slip beneath it, a process
known as invagination.

 Once the cells have invaginated, some displace

the hypoblast, creating the embryonic
endoderm, and others come to lie between the
epiblast and newly created endoderm to form
mesoderm. Cells remaining in the epiblast then
form ectoderm
 Day 15
Formation of the Primitive Streak
In order to gastrulate cells must lose
their connections with other cells and
extracellular matrix and migrate out of
the epithelium

The signals that cause this and which cells

respond are not well understood.
 Epiblast cells move through the primitive streak,
They Gastrulate
1st) Ingressing Epiblast cells
2nd) Mesoderm formed
Displace the hypoblasts
Pseudopodia

Day 16

Three Germ layers formed

 Ctd’
 As more and more cells move into mesodermal layer,
they begin to spread laterally and cephalad
 They migrate beyond the margin of the disc and
establish contact with the extraembryonic mesoderm
covering the yolk sac and amnion.
 Two small tightly adherent areas of newly formed
ectoderm and endoderm form cranially and caudally
i.e.buccopharyngeal membrane -cranially and cloacol
membrane
 The first cells that migrate cephalic to the streak form
the prechordal plate - That forms between the tip of
the notochord and the buccopharyngeal membrane
 Trilaminar germ disc
Three germ layers: Ectoderm, Mesoderm, and Endoderm

Cells that migrate

through the primative
pit become the
prechordal plate later
the notochordal
process
Movement of
Gastrulating
Mesoderm.
Blue in/red
through
 Formation of the notochord
 Prenotochordal cells invaginating in the
primitive pit move forward cephalad until they
reach the prechordal plate and become
intercalated in the hypoblast so that for a
short time the midline of the embryo consists
of two cell layers that form the notochordal
plate
 As the hypoblast is replaced by endoderm
cells moving in at the streak, cells of the
notochordal plate proliferate and detach from
the endoderm and form a solid cord of cells-
the definitive notochord
Formation of notochord
 Notochord formation ctd’
 The notochord underlies the neural tube and
serves as the basis for the formation of axial
skeleton
NB> the notochord is a dynamic process, with
the cranial end forming first and caudal
regions are added as the primitive streak
assumes a More caudal position.
 The notochord and prenotochordal cells
extend cranially to the prechordal plate (an
area just caudal to the buccopharyngeal
membrane) And caudally to the primitive pit.
 Day 17
Formation of the notochordal process and the prechordal plate
From cells that migrated through the primative pit

Important transient signaling structure: secretes numerous signals

Hollow tube
Ctd’
 At the point where the pit forms an
indentation in the epiblast, a neurenteric
canal temporarily connects the amniotic
and yolk sac cavities
 Around the 16th day of development
near the cloacal membrane on the wall
of the yolk sac a small diverticulum
forms that extends into the connecting
stalk. This diverticulum is called the
allanto-enteric diverticulum/or allantois,
The neuroenteric canal and the allantois
 NB

 NB> allantois serves as a reservoir for

excretion products of the renal
System in other animals but, in humans it
remains rudimentary and if it persists it is a
common cause of abnormalities of bladder
development
 Day 17
Formation of the notochordal process and the prechordal plate
From cells that migrated through the primative pit

Important transient signaling structure: secretes numerous signals

Hollow tube
Establishment of the body axis
 Establishment of the body axes, anteroposterior,
dorsoventral, and left-right, takes place before and
during the period of gastrulation

 The anteroposterior axis is signaled by cells at the

anterior (cranial) margin of the embryonic disc. –the
anterior-visceral-endoderm (AVE),expresses gene
OTX2, LIM1, and HESX1 essential for head formation.

 Once the streak is formed, a number of genes

regulate formation of dorsal and ventral mesoderm
and head and tail structures
Fate Map of cells Established During Gastrulation

Cells of the epiblast that migrate and ingress through the

primitive streak have been mapped and their ultimate fates
determined as follows:-
1. Cells that ingress through the cranial region of the node
become notochord;
2. Cells migrating at the lateral edges of the node and from
the cranial end of the streak become paraxialmesoderm;
3. those migrating through the mid-streak region become
intermediate mesoderm;
4. those migrating through the more caudal part of the streak
form lateral plate mesoderm;
5. cells migrating caudal-most part of the streak contribute to
extraembryonic mesoderm (the other source of this tissue is
the primitive yolk sac [hypoblast]
Growth of the Embryonic Disc
 Grows more cephalad by proliferetion and
migration of the epiblastic cells through steak-
up to the end of 4th week
 The streak shows regressive changes, and
soon disappears
 Sacrococcygeal Teratoma - Remnants of the
primitive streak that persists in the distal portion and
contain tissues derived from all three germ layers in
incomplete stages of differentiation. They are the
most common tumor in newborns and have an
incidence of approximately one in 35,000; most
affected infants (80%) are female.
Sacroccocygeal teratoma
Third week to 8th week of
embryonic development
 Next lecture –please read
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