Developmental Biology

Introduction

Mesut Muyan
Phone: 7653
E-mail: [email protected]
Developmental biology is the science that
provides explanations how the structure of
organisms changes with time.
In any animal the sperm and eggs and their precursor
cells are known as the germ line. All other cell types are
called somatic cells.

The germ-line cells have to retain a full complement of

genes.

All the somatic cells also contain the full complement of

genes and that the differences between cells are due to
the fact that different subsets of genes are active.
• Both sexes have specialized organs to carry out sexual
reproduction.

• Females produce ovum (ova=plural) in the ovaries and

Males produce spermatozoon (spermatozoa=plural) in the
testes.

• A zygote is formed when a spermatozoon fertilizes an

ovum, which develops into embryo for birth
Sexual development is programmed by the genome.
 Sex Determination Is Directed By Our
Genome

• Humans have 23
pairs of
chromosomes
– 22 pairs of
autosomes
– X and Y = 1 pair of
sex chromosomes

Figure 26-1
The two sex chromosomes designated as X or Y, contain
genes that direct the development of internal and external
sex organs. The X chromosome is larger than Y
and includes many genes that are missing in Y chromosome.
X and Y Chromosomes Determine Genetic Sex

Figure 26-2
Sexual reproduction means that the life cycle involves the
union of male and female gametes to form a fertilized
egg or zygote. Male gamete is spermatozoon
(sperm), and the female gamete is an egg or ovum.

Each gamete contributes a haploid (1n) chromosome set

so the zygote is diploid (2n), containing a maternal- and a
paternal-derived copy of each chromosome.

The gametes are formed from germ cells in the embryo.

The germ cells are referred to collectively as the germ line,
consisting of cells that will or can become the future
gametes, and all other cells are referred to as the somatic
tissues or soma. The importance of the germ line is that
its genetic information can be passed to the next
generation, while that of the soma cannot.
GAMETOGENESIS
Mitosis: Germ Cell Proliferation
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia

Reproductive adult
Reproductive adult

Figure 26-5, step 1

 Meiosis: DNA Replicates
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia
MEIOSIS
2 DNA replicates
Primary but no cell division. Primary
Sister Sister
oocyte spermatocyte
chromatids 46 chromosomes, chromatids
duplicated

Reproductive adult
Reproductive adult

Figure 26-5, steps 1–2

 First Meiotic Division
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia
MEIOSIS
2 DNA replicates
Primary but no cell division. Primary
Sister Sister
oocyte spermatocyte
chromatids 46 chromosomes, chromatids
duplicated

Reproductive adult
3 First meiotic
First division
Secondary
polar Primary gamete divides Secondary
oocyte
body into two secondary gametes. spermatocytes
(egg)
Reproductive adult

23 chromosomes,
duplicated

Figure 26-5, steps 1–3

 Second Meiotic Division
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia
MEIOSIS
2 DNA replicates
Primary but no cell division. Primary
Sister Sister
oocyte spermatocyte
chromatids 46 chromosomes, chromatids
duplicated

Reproductive adult
3 First meiotic
First division
Secondary
polar Primary gamete divides Secondary
oocyte
body into two secondary gametes. spermatocytes
(egg)
Reproductive adult

(may not 23 chromosome,

occur)

4 Second meiotic Spermatids

Disintegrates division
Egg released Secondary gamete divides. develop into
from ovary at 23 chromosomes
ovulation. (haploid) Sperm

One primary spermatocyte

yields 4 sperm.

Figure 26-5, steps 1–4

 Ovulation Without Fertilization
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia
MEIOSIS
2 DNA replicates
Primary but no cell division. Primary
Sister Sister
oocyte spermatocyte
chromatids 46 chromosomes, chromatids
duplicated

Reproductive adult
3 First meiotic
First division
Secondary
polar oocyte Primary gamete divides Secondary
body (egg) into two secondary gametes. spermatocytes
Reproductive adult

(may not 23 chromosomes,

occur) duplicated

4 Second meiotic Spermatids

Disintegrates division
Egg released Secondary gamete divides. develop into
from ovary at 23 chromosomes
ovulation. (haploid) Sperm

One primary oocyte One primary spermatocyte

yields 1 egg. yields 4 sperm.

Unfertilized egg
passes out of body.
Figure 26-5, steps 1–5
Ovulation with Fertilization Is Followed by
Final Step of Meiosis
FEMALE STAGE OF CELL DIVISION MALE

Oögonium 1 MITOSIS Spermatogonium

Germ cell proliferation

Embryo
46 chromosomes
per cell (only two
shown here)

Embryo
46
Oögonia (diploid)
Spermatogonia
MEIOSIS
2 DNA replicates
Primary but no cell division. Primary
Sister Sister
oocyte spermatocyte
chromatids 46 chromosomes, chromatids
duplicated

Reproductive adult
3 First meiotic
First division
Secondary
polar oocyte Primary gamete divides Secondary
body (egg) into two secondary gametes. spermatocytes
Reproductive adult

(may not 46 chromosomes,

occur)

4 Second meiotic Spermatids

Disintegrates division
Egg released Secondary gamete divides. develop into
from ovary at 23 chromosomes
ovulation. (haploid) Sperm

6 FERTILIZATION
One primary oocyte One primary spermatocyte
yields 1 egg. yields 4 sperm.

5
Second
polar body
disintegrates.
Unfertilized egg
passes out of body. Zygote
Figure 26-5, steps 1–6
Meiosis is the first step in gametogenesis: separation of
Homologous chromosomes into haploid daughter cells
Spermatogonia and oogonia are the germ cells that will
eventually develop into the mature sperm or egg
Primary spermatocyte or oocyte: the duplication of
homologous chromosomes to get ready for meiosis
Secondary spermatocyte or oocyte: the first meiotic
division separates the homologous chromosomes from
each parent
Spermatids or eggs: the second meiotic division
separates the 2 chromatids and creates 4 haploid cells.
In males, this eventually produces 4 sperm cells by the
process of spermiogenesis. In females, it produces 1
egg and 3 polar bodies. This allows the egg to retain
more cytoplasm to support early stages of development.
Spermatocytes to Spermatids

Figure 28.8b, c
 Spermatogenesis: Spermatids to Sperm

• Late in spermatogenesis, spermatids are haploid but are

nonmotile
• Spermiogenesis – spermatids lose excess cytoplasm and
form a tail, becoming sperm
• Sperm have three major regions
– Head, contains DNA and acrosome containing
hydrolytic enzymes that allow the sperm to penetrate
and enter the egg
– Midpiece, contains mitochondria spiraled around the tail
filaments
– Tail, a typical flagellum produced by a centriole
Spermatogenesis: Spermatids to Sperm

Figure 28.9a
 Sertoli Cells
• Cells that extend from the basal lamina to the
lumen of the tubule that surrounds developing
cells
• They are bound together with tight junctions
forming an unbroken layer with the
seminiferous tubule, dividing it into two
compartments
– The basal compartment – contains spermatogonia
and primary spermatocytes
– Adluminal compartment – contains meiotically
active cells and the tubule lumen
 Leydig Cells

• Their tight junctions form a blood-testis barrier

• This prevents sperm antigens from escaping
through the basal lamina into the blood
• Since sperm are not formed until puberty, they
are absent during thymic education
• Spermatogonia are recognized as “self” and are
influenced by bloodborne chemical messengers
that prompt spermatogenesis
Adluminal Compartment Activities
• Spermatocytes and spermatids are nearly
enclosed in sustentacular cells, which:
– Deliver nutrients to dividing cells
– Move them along to the lumen
– Secrete testicular fluid that provides the transport
medium for sperm
– Dispose of excess cytoplasm sloughed off during
maturation to sperm
– Produce chemical mediators that help regulate
spermatogenesis
Accessory Glands Contribute to Semen
• Accessory glands contribute 99% of semen volume, as well
as the following
– Seminal vesicles – fructose, vitamin C, prostaglandins
– Prostate gland – buffers, citric acid, enzymes
– Bulbourethral gland – mucus, buffers
http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes
Fertilization is the fusion of female and
male gametes to form zygote with
diploid number of chromosomes
Spermatozoa have two roles to play during
fertilization:
(1) contribution of a haploid set of chromosomes required
for normal development.

(2) Triggering oocyte activation and subsequent

initiation of metabolic events to support embryonic
development
*Mammalian spermatozoa are not fertile when they
leave the male reproductive tract, even though they are
immediately motile.

*Spermatozoa require a species-dependent period of

time to undergo complex changes, collectively referred
to as 'capacitation' that transform them from non
fertilizing to potentially fertilizing cells
Capacitation is characterized as a complex of structural
and functional changes occurring in spermatozoa that:

(1) begins after the removal of stabilizing factors acquired

by spermatozoa while resident in seminal plasma;

(2) proceeds throughout sperm transit in the female

reproductive tract

(3) is considered to be complete when spermatozoa are

able to respond to zona pellucida ligands by undergoing
the acrosome reaction
102

107

Suarez S , Pacey A A Hum. Reprod. Update 2006;12:23-37

ACE: angiotensin I converting enzyme (peptidyl-dipeptidase A); an endomannosidase
GPI: Glycosylphosphatidylinositol

Nature Structural & Molecular Biology 12, 107 - 108 (2005)

Consequences of Capacitation

*Increased rate of metabolism

*Flagellum beats more rapidly, resulting in more

motile spermatozoa

*Changes in sperm glycoproteins allow sperm-egg

binding

*Pro-Acrosin (inactive) is converted to acrosin

(active)
*Chemotaxis: In the capacitated state, spermatozoa can
then respond to molecular signals provided by the oocyte
and associated cellular complexes (cumulus cells, zona
pellucida). This sets the stage for the acrosome reaction.
Sperm-Egg Recognition & Binding

• Sperm contacts zona pellucida

• Sperm-egg binding occurs: Receptors on post-acrosomal

membrane bind to ZP3

• ZP3 and sperm-receptors are clustered away from contact

site

• Acrosin digests pathway through zona and may assist in

binding via ZP2

• ZP2-sperm binding holds sperm in place as it works its way

through the zona
Acrosome Reaction:

*Acrosome reaction is an exocytotic event leading

to the release of enzymes that aid penetration of
the zona pellucida and to the acquisition of
properties by the sperm head plasma membrane
that permit fusion with the oocyte.
Acrosomal Enzymes:
*Acid Proteinase: a general protease that hydrolyzes
proteins at an acid pH

*Hyaluronidase: a protease that digests hyaluronan, a

viscous constituent of the interstitial barrier, in the
cumulus oophorus cells

*Collagenase: a protease that digests collagen

*Acrosin: A special human acrosomal serine protease

that digests zona pellucida proteins may also mediate
spermatozoa-ZP binding
Acrosome reaction is initiated by the interaction
with Zona Pelluciada (ZP) proteins on ZP of the
ovum and the ZP Receptors on the spermatozoa.
Zona Pellucida (ZP)

• Protein coat surrounding egg

• Species-specific barrier to sperm binding and penetration;

keeps sperm of foreign species out

• ZP is not 100% effective; some cross-species fertilization can

occur (e.g., horse & donkey = mule)

• Remove the ZP and other species sperm can fertilize and egg
(e.g., human sperm can fertilize the zona-less hamster egg)
*During mammalian fertilization, the zona pellucida
(ZP) matrix surrounding the oocyte is responsible for
the binding of the spermatozoa to the oocyte and
induction of the acrosome reaction (AR) in the ZP-
bound spermatozoon. The AR is crucial for the
penetration of the ZP matrix by spermatozoa.
Acrosome reaction: relevance of zona pellucida glycoproteins
Satish K Gupta and Beena Bhandari
http://tspacetest.library.utoronto.ca:8080/html/1778/11640/l8.htm
Each sperm has galactosyl transferase (GalTase) enzymes on its head
• Galactosyl transferase is an enzyme that transfers a galactosyl group from
one molecule to another
• Egg has ZP3 in ZP
• GalTase on the sperm surface acts as the receptor for ZP3 because it binds
galactose on ZP3 (ZP3 is a glycoprotein with some of the sugar residues in
the carbohydrate portion being galactose residues)
• At binding, the cortical granules are intact
• Acrosome is is also intact
• The receptors on the sperm head cluster together as calcium levels increase in
the sperm cell cytoplasm

• Calcium is a known mediator of biomembrane fusion and this increase of

intracellular calcium plays a role in the fusion of the acrosomal membrane with
the sperm cell membrane causing vesicles to form

• This vesiculation allows the contents of the acrosome to flow out

• The enzymes begin to digest the zona pellucida

Reviews of Reproduction (1997) 2, 165–174
Spermatozoa and Ovum fusion
ADAM: A Disintegrin And Metalloprotease
http://www.nature.com/fertility/content/fig_tab/ncb-nm-fertilitys57_f3.html
PLC: Phospholipase C
DAG: Diacylglycerol
PIP2: Phosphatidylinositol 4,5-
bisphosphate
Science 316 (5823): 407-408
Cortical Granules

The cortical granules are membrane bound vesicles

that lie just below egg cell membrane

*CGs contain many enzymes for protein, carbohydrate digestion

*CGs undergo exocytosis at fertilization

*Enzymes contained in the cortical granules will digest the

proteins of the zona pellucida (i.e., ZP3, ZP2) to prevent
more sperm binding which could lead to polyspermy
Cortical Granule Content

-Protease
-Glycoconjugates
-Glucosaminidase
http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch12/DBNGerm.htm
l

http://www.ehd.org/virtual-human-embryo/figure.php?stage=1&figure=19
http://tspacetest.library.utoronto.ca:8080/html/1778/11640/l8.htm
Sequence of events for spermatozoon and ovum fusion

*Acrosome Intact Sperm Contacts Corona Radiata

*Acrosome Vesiculates: Enzymes are Released

*Sperm Binds to Zona Pellucida at Post-Acrosomal Region

and enzymes Continue to Digest Route to Egg

*Sperm-Egg Membrane Contact & Fusion

*Sperm Nucleus Enter Egg Cytoplasm

Pronuclear Events

When the sperm enters, the egg is released from meiotic

arrest and will complete meiosis II prior to the fusion
of the pronuclei.

*Haploid egg pronucleus awaits for the spermatozoa to

activate the egg

*The haploid sperm nucleus enters and becomes

the sperm pronucleus

*Sperm pronucleus swells, migrates towards

the egg pronucleus

*The pronuclei will fuse

 Sperm and Egg Fuse to Form a Zygote

First polar
body

Egg

Sperm
nucleus

Sperm and Sperm nucleus

egg plasma moves into
membranes fuse. cytoplasm of egg.

HUMAN PHYSIOLOGY, An Integrated Approach, 5th Edition, By Dee Unglaub Silverthorn, Pearson International Edition
Pronuclear Fusion

*When they are in close proximity, the pronuclear envelopes

vesiculate: the nuclear membranes break up to form a
circle of smaller vesicles that surround the chromatin of
each nucleus

*The chromatin from each pronucleus intermixes to form

the diploid zygote nucleus

*The nuclear envelope reforms around the zygote nucleus

and embryonic development will begin with the onset of
cleavage (cell divisions of the zygote).
 Oocyte Completes Meiosis and Nuclei Fuse

Sperm
nucleus Second
Egg polar body

Oocyte nucleus Sperm and egg

completes meiotic nuclei fuse to
division. form zygote nucleus.

HUMAN PHYSIOLOGY, An Integrated Approach, 5th Edition, By Dee Unglaub Silverthorn, Pearson International Edition