FERTILIZATION

• The fertilization process is the series of

biological steps that lead to the union of male
and female gametes (sperm and egg),
resulting in the formation of a zygote—the
first cell of a new organism. This process
occurs in sexually reproducing organisms and
is highly regulated.
 Ovulation

• Around day 14 of a typical 28-day menstrual

cycle, a mature egg (secondary oocyte) is
released from the ovary into the fallopian
tube (also called oviduct).
• The egg is surrounded by protective layers:
the corona radiata (outer) and zona pellucida
(inner glycoprotein layer).
 Sperm Transport
• During sexual intercourse, millions of sperm
are ejaculated into the female reproductive
tract.
• Sperm travel through the cervix → uterus →
fallopian tubes.
• Out of millions, only a few hundred sperm
reach the site of the egg (usually the ampulla
of the fallopian tube).
 Capacitation
• As sperm travel through the female
reproductive tract, they undergo capacitation,
a series of biochemical changes.
• This process:
– Removes inhibitory proteins from the sperm head.
– Increases sperm motility.
– Prepares the sperm for the
Acrosome reaction.
 Acrosome Reaction
• When a capacitated sperm contacts the zona
pellucida, it releases enzymes (from the
acrosome, a cap-like structure).
• These enzymes (like hyaluronidase and
acrosin) digest the zona pellucida, allowing the
sperm to penetrate toward the egg
membrane.
Sperm-Egg Fusion

• Once a single sperm penetrates the zona

pellucida, its plasma membrane fuses with
the egg’s plasma membrane.
• The sperm head and tail enter the egg
cytoplasm.
• The egg undergoes a cortical reaction: vesicles
under the egg’s membrane release enzymes
that harden the zona pellucida, blocking
polyspermy (entry of more than one sperm).
 Completion of Meiosis II
• Before fertilization, the egg is arrested in
metaphase II of meiosis.
• Upon sperm entry, the egg completes meiosis
II, releasing the second polar body, and
forming a mature ovum
 Formation of Pronuclei
• The sperm nucleus decondenses to form the
male pronucleus.
• The female pronucleus also forms from the
egg nucleus.
• The two pronuclei migrate toward each other
and their membranes dissolve.
 Syngamy (Fusion of Genetic Material)

• The chromosomes from the male and female

pronuclei align and fuse.
• This restores the diploid number (46
chromosomes in humans).
• The result is a zygote, the first diploid cell of
the new organism.
 Zygote Formation and First Cleavage
• The zygote soon undergoes its first mitotic
division (cleavage), starting embryonic
development.
• The embryo continues to divide as it moves
toward the uterus for implantation.
 CONCEPTION
• Conception is the process by which a sperm
cell from a male and an egg cell from a
female combine to form a zygote, initiating
pregnancy. It includes the entire process from
ovulation to implantation of the embryo in
the uterus.
 Sperm Deposition and Migration
During sexual intercourse, millions of sperm are
deposited in the vagina.
• Sperm travel:
• Through the cervix,
• Into the uterus,
• Then into the fallopian tubes.
• Only hundreds out of millions make it near
the egg.
 Fertilization
• Fertilization typically occurs in the ampulla,
the widest part of the fallopian tube.
 Cleavage (Early Cell Division)
• The zygote begins dividing via mitosis while
moving through the fallopian tube.
• 2-cell → 4-cell → 8-cell → morula (solid ball)
→ blastocyst (hollow structure).
• No increase in overall size—just division into
smaller cells (blastomeres).
 Blastocyst Formation
• Around day 5–6, the embryo becomes a
blastocyst:
• Trophoblast (outer layer) → forms placenta.
• Inner Cell Mass (ICM) → forms the baby.
• Blastocoel: fluid-filled cavity.
 Implantation
• Around day 6–10 after fertilization, the blastocyst
reaches the uterus.
• It attaches to the endometrial lining (the inner wall
of the uterus).
• The trophoblast invades the endometrium and
secretes hCG (human chorionic gonadotropin):
– hCG maintains the corpus luteum, which keeps producing
progesterone to maintain the uterine lining.
• Successful implantation marks the true moment of
conception, as it initiates pregnancy.
 Key Events and Timing
• Event - Approximate Day After Last Period
• Ovulation Day- 14
• Fertilization Day- 14–15
• Zygote Formation- Day -15
• Blastocyst Formation Day- 19–20
• Implantation Day- 20–24
 Important Hormones in Conception
• Estrogens: Prepares uterine lining before
ovulation.
• LH (Luteinizing Hormone): Triggers ovulation.
• Progesterone: Maintains the uterine lining
after ovulation.
• hCG: Secreted by trophoblast post-
implantation, supports early pregnancy.
 IMPLANTATION
• The implantation of the blastocyst—is a
crucial early step in human pregnancy. It
occurs when a fertilized egg (zygote), now
developed into a blastocyst, attaches to and
embeds itself into the uterine lining
(endometrium) to begin forming the placenta
and eventually a fetus.
 Stages of Fetal Implantation
Fertilization (Day 0)
• Occurs in the ampulla of the fallopian tube.
• A sperm fertilizes an egg, forming a zygote.

Cleavage and Development (Day 1–5)

• The zygote divides into multiple cells (cleavage).
• It becomes a morula (solid ball of cells), then a blastocyst
(hollow structure with fluid inside).

Blastocyst Arrival in Uterus (Day 5–6)

• The blastocyst reaches the uterus around 5–6 days after
fertilization.
• It remains free-floating for about a day, preparing to implant.
 Implantation Proper (Day 6–10 after
Fertilization)
Step-by-Step Breakdown:
a. Apposition
• The blastocyst loosely aligns with the endometrial
epithelium (uterine lining).
• Positioning is usually in the upper posterior wall of the
uterus.

b. Adhesion
• Specialized outer cells of the blastocyst called trophoblasts
attach to uterine epithelial cells.
• This marks the start of actual implantation.
Invasion
• The trophoblasts invade the endometrium.
• They differentiate into:
– Cytotrophoblasts: Inner layer (proliferating cells)
– Syncytiotrophoblasts: Outer layer (invasive and hormone-
secreting)

Embedding
• The blastocyst becomes fully embedded in the
endometrium by day 9–10.
• The endometrial tissue grows over it, completing
implantation.
 EMBRYOLOGICAL DEVELOPMENT
• Embryological development is the process by
which a fertilized egg transforms into a
complex multicellular organism—a baby. This
process occurs in distinct stages and involves
precise cell divisions, differentiation, and
morphogenesis
Fertilization
• Occurs in the ampulla of the fallopian tube.
• A sperm cell penetrates the oocyte → forms a
zygote (diploid).
• This marks Day 0 of embryonic development.

Cleavage (Days 1–3)

• Rapid mitotic cell divisions without growth.
• Zygote → 2-cell → 4-cell → 8-cell → 16-cell stage
(called morula).
• Still enclosed in the zona pellucida (protective shell).
Blastocyst Formation (Days 4–5)
• Fluid enters the morula → forms a blastocyst.
• Blastocyst has:
– Inner Cell Mass (ICM) → forms the embryo.
– Trophoblast → forms placenta and foetal membranes.
– Blastocoel → fluid-filled cavity.

Implantation (Days 6–10)

• The blastocyst attaches to the endometrium and embeds
itself.
• Trophoblasts differentiate:
– Cytotrophoblast: cellular layer.
– Syncytiotrophoblast: invasive, secretes hCG.
Bilaminar Disc Stage (Week 2)
• Inner Cell Mass becomes:
– Epiblast: forms the embryo.
– Hypoblast: contributes to extra embryonic
membranes.
• Amniotic cavity and yolk sac form.

Gastrulation (Week 3) – Formation of Germ Layers

• Most critical event in development.
• Primitive streak forms on the epiblast.
• Epiblast cells migrate inward → form three germ layers:
– Ectoderm → skin, brain, nerves.
– Mesoderm → muscles, bones, heart, blood.
– Endoderm → gut lining, lungs, liver.
Neurulation (Late Week 3 – Week 4)
• Formation of the neural tube from ectoderm → becomes the
brain and spinal cord.
• Neural crest cells → give rise to peripheral nerves, facial
structures, melanocytes.

Organogenesis (Weeks 4–8)

• Formation of major organ systems:
– Heart begins beating ~Day 22.
– Limb buds, eyes, ears, gut, and lungs begin forming.
– Pharyngeal arches appear (face, neck development).
• Embryo becomes recognizable as human by Week 8.
Embryo to Foetus Transition (End of Week 8)
• Now called a foetus.
• All major organs are present, but not yet fully
functional.
Germ Layers and What They Form
Germ Layer Derivatives
• Ectoderm CNS (brain, spinal cord), PNS,
skin, hair, nails, eyes, enamel
• Mesoderm Muscles, bones, heart,
kidneys, blood vessels,
reproductive organs
• Endoderm Lining of GI tract, liver,
pancreas, lungs, bladder
 Embryological Timeline
Week Key Events
• 1 Fertilization cleavage, blastocyst
formation
• 2 Implantation, bilaminar disc
• 3 Gastrulation, formation of germ layer
• 4 Neurulation, early organ development
• 5–8 Rapid organogenesis, limb formation
• 9+ Transition to foetal stage, organ
maturation begins
 PLACENTA
• The placenta is a temporary but vital organ
that develops in the uterus during pregnancy.

• It plays a central role in supporting the

developing foetus by facilitating nutrient and
gas exchange, waste elimination, and
hormone production.
 Placental Development
Fertilization and Early Development (Day 0–5)
• Fertilization occurs in the fallopian tube,
forming a zygote.
• The zygote undergoes cleavage to become a
morula (16-cell stage).
• The morula develops into a blastocyst by Day 5:
– Inner Cell Mass (embryoblast) → embryo
– Outer Cell Layer (trophoblast) → placenta
 Implantation and Trophoblast
Differentiation (Day 6–10)
• The blastocyst implants into the
endometrium (uterine lining).
• The trophoblast differentiates into two layers:
– Cytotrophoblast: Inner mononuclear layer
– Syncytiotrophoblast: Outer multinucleated layer
that invades maternal tissue and establishes early
nutrient exchange.
Formation of Primary Villi (Day 11–13)
• Finger-like projections of cytotrophoblasts
grow into the syncytiotrophoblast.
• These are known as primary chorionic villi.
Secondary Villi Formation (Day 16–18)
• Extra embryonic mesoderm invades the core
of the primary villi.
• These mesodermal cores give rise to
connective tissue, forming secondary villi.
Tertiary Villi Formation (~Day 20 onwards)

• Blood vessels develop within the mesodermal

core of the secondary villi.
• These vessels connect to the fetal heart via
the umbilical cord, forming tertiary villi.
• The placenta is now capable of maternal-fetal
exchange.
Establishment of Maternal Circulation (End
of Week 3)
• The syncytiotrophoblast erodes maternal
capillaries, forming lacunae (blood-filled
spaces).
• These lacunae connect, allowing maternal
blood to flow through the intervillous spaces.
 Chorion Differentiation (End of Week 4)

• The chorion is made of:

– Chorionic plate (fetal surface of the placenta
where the umbilical cord attaches)
– Chorionic villi
• The villi regress in areas not involved in
implantation and persist where the placenta
will form (chorion frondosum- portion of
chorion that forms placenta).
 Formation of the Decidua (Maternal
Component)
• The endometrium undergoes decidual
reaction: stromal cells become large and
glycogen-rich.
• It’s divided into:
• Decidua basalis: directly under the implanted
embryo, forms maternal part of placenta.
• Decidua capsularis: surrounds the embryo.
• Decidua parietalis: lines the rest of the uterus.
Maturation of the Placenta (Weeks 12–40)

• By end of the first trimester, the placenta is fully formed.

• Maternal and foetal blood do not mix—they are
separated by the placental barrier, which includes:
– Syncytiotrophoblast
– Cytotrophoblast
– Basement membrane
– Foetal capillary endothelium
• As gestation progresses:
– Cytotrophoblasts become thinner or disappear.
– Surface area increases for better exchange.
– Villi branch extensively.
 Umbilical Cord Formation
• Connects fetus to placenta.
• Contains:
– 2 umbilical arteries (carry deoxygenated blood
from fetus to placenta)
– 1 umbilical vein (carries oxygenated blood to
fetus)
– Surrounded by Wharton's jelly (a protective
gelatinous substance)
 Maternal-Fetal Interface
• Exchange of gases, nutrients, and waste
occurs in intervillous spaces, where maternal
blood bathes the villi.
• Placental blood flow is maintained by
maternal spiral arteries and fetal umbilical
vessels.
 FUNCTIONS OF THE PLACENTA
Respiratory Function
• The placenta acts like fetal lungs, allowing gas
exchange between maternal and fetal blood.
• Oxygen transfer: Oxygen diffuses from
maternal blood (in the intervillous space) to
fetal blood (in chorionic villi).
• Carbon dioxide removal: CO₂ diffuses from
fetal blood into maternal circulation for
excretion.
 Nutritional Function
The placenta supplies the fetus with essential
nutrients:
Nutrient Mode of Transport
• Glucose Facilitated diffusion
• Amino acids Active transport
• Fatty acids Passive
diffusion
• Vitamins Active and passive
• Water & Electrolytes Osmosis and active transport
 Excretory Function
• Removes fetal metabolic waste products by
transferring them to the maternal blood:
• Urea
• Creatinine
• Bilirubin
• Carbon dioxide
➡️These are filtered and excreted by the
maternal kidneys.
 Endocrine (Hormonal) Function
The placenta produces several hormones vital for maintaining
pregnancy:

hCG (human chorionic gonadotropin)

• Produced early in pregnancy.
• Maintains the corpus luteum to continue secreting progesterone.
• Basis of pregnancy tests.

Progesterone
• Initially secreted by corpus luteum, then by placenta (from ~10
weeks).
• Maintains endometrial lining.
• Suppresses uterine contractions.
Estrogens
• Promotes uterine growth and blood flow.
• Enhances breast development.

hPL (human placental lactogen)

• Modifies maternal metabolism
• Induces insulin resistance in the mother (to increase
glucose for foetus).
• Stimulates breast development.
 Immune Function
• The placenta plays a dual role in protecting the fetus:

a. Immunological barrier:
• Prevents maternal immune system from rejecting the
fetus .
b. Passive immunity:
• Transfers maternal IgG antibodies (especially in 3rd
trimester) to the fetus.
• Provides temporary immunity to newborn against
infections like measles, tetanus, etc.
 Barrier Function
• Limits passage of certain substances, protecting the
fetus from toxins and pathogens.
• However, some harmful substances can cross:
– Alcohol
– Nicotine
– Some drugs (e.g. thalidomide)
– Viruses (e.g. rubella, HIV)
– Bacteria (rarely)
• ➡️Known as teratogens if they interfere with fetal
development.
Hematopoietic Function (Early Pregnancy)

• In early gestation, the placenta helps in blood

cell formation before the fetal liver and bone
marrow are fully functional.
 Metabolic Function
• The placenta itself metabolizes glucose, fatty
acids, and amino acids to meet its own energy
needs.
• Synthesizes cholesterol, hormones, and some
proteins.
 FETAL GROWTH AND DEVELOPMENT
• Fetal growth and development is a complex,
highly regulated process that occurs over
approximately 40 weeks of gestation, divided
into three trimesters.
 Stages of Prenatal Development
Germinal Stage (Weeks 1–2)
• Fertilization: Occurs in the fallopian tube; a
zygote is formed.
• Cell Division: The zygote undergoes rapid
mitotic divisions (cleavage).
• Blastocyst Formation: By day 5, a hollow ball of
cells (blastocyst) is formed.
• Implantation: Around days 6–10, the blastocyst
implants into the uterine wall.
Embryonic Stage (Weeks 3–8)
• Gastrulation: Formation of three germ layers: ectoderm,
mesoderm, and endoderm.
• Neurulation: Neural tube (future brain and spinal cord)
begins to form.
• Organogenesis: Major organs and structures begin to
form:
• Heart starts beating (~week 5).
• Limb buds appear.
• Eyes and ears begin forming.
• Placenta starts to form and take over hormonal support.
Fetal Stage (Weeks 9–40)
• This stage is marked by rapid growth,
maturation of organs, and preparation for
birth.
 Trimester-Wise Development
First Trimester (Weeks 1–12)
• Weeks 9–12 (Early Fetal Period):
• Head is half the size of the fetus.
• Eyelids close.
• External genitalia begin to show sex
differentiation.
• Kidneys begin to produce urine.
Second Trimester (Weeks 13–26)
• Weeks 13–16:
• Rapid growth in body length.
• Limb movements become more coordinated.
• Bones start to harden.
• Weeks 17–20:
• Lanugo (fine hair) and vernix caseosa (protective skin coating) form.
• Mother may feel fetal movements (quickening).
• Weeks 21–26:
• Lungs start producing surfactant.
• Fetus may respond to sound.
• Significant brain growth occurs.
Third Trimester (Weeks 27–40)
• Weeks 27–32:
• Fetus gains significant fat.
• Bones fully developed but soft.
• Sleep-wake cycles begin.
• Weeks 33–36:
• Lungs and other organs near maturity.
• Suckling reflex develops.
• Weeks 37–40:
• Full-term fetus.
• Fat continues to accumulate.
• Head may engage (move into pelvis).
Factors Influencing Fetal Development

•Genetics
•Nutrition (e.g., folic acid, iron)
•Maternal health and infections
•Teratogens (e.g., alcohol, drugs, radiation)
•Placental function
 FETAL CIRCULATION
• Fetal circulation refers to the specialized
circulatory system of the fetus that allows
oxygenated blood from the placenta to bypass
the non-functioning fetal lungs and liver, while
delivering oxygen and nutrients to vital organs
like the brain and heart.
 Shunts in Fetal Circulation
• Fetal circulation includes three physiological
shunts that temporarily reroute blood to
ensure proper oxygen and nutrient delivery
while bypassing non-functional organs like
the lungs and liver.
1. Ductus Venosus
• Location: Between the umbilical vein and the
inferior vena cava (IVC).
• Function: Bypasses the liver, allowing oxygen-rich
blood from the placenta to flow directly into the
IVC.
• Oxygenated Blood: Maximizes delivery to the heart
and brain.
• Closure After Birth: Becomes the ligamentum
venosum.
Foramen Ovale
• Location: Opening between the right and left atria of
the heart.
• Function: Allows blood to bypass the right ventricle and
lungs by flowing directly from the right atrium to the
left atrium.
• Purpose: Sends the most oxygenated blood to the brain
and upper body via the left heart and ascending aorta.
• Closure After Birth: Functionally closes due to pressure
changes and becomes the fossa ovalis.
Ductus Arteriosus
• Location: Connects the pulmonary artery to the
descending aorta.
• Function: Diverts most blood away from the non-
functioning lungs into the systemic circulation.
• Oxygen Level: Blood here is moderately oxygenated.
• Closure After Birth: Constricts and forms the
ligamentum arteriosum, usually within 1–2 days.
FETAL CIRCULATION SHUNTS
 STEP-BY-STEP FLOW OF FETAL BLOOD
Placenta to Fetus
• Oxygenated, nutrient-rich blood travels from the
placenta via the umbilical vein.
• This blood has an oxygen saturation of ~80% (very high
for fetal blood).

Liver Bypass – Ductus Venosus

• Most of this blood bypasses the liver through the
ductus venosus and enters the inferior vena cava (IVC).
• A small amount perfuses the liver directly.
Inferior Vena Cava to Right Atrium
• The IVC delivers a mix of oxygenated (from placenta) and
deoxygenated (from lower body) blood to the right atrium.

Right Atrium to Left Atrium – Foramen Ovale

• Most oxygen-rich blood is shunted through the foramen
ovale into the left atrium, bypassing the right ventricle and
pulmonary circulation.
• This blood then moves to the left ventricle and is pumped
into the aorta, supplying the brain and heart with the most
oxygenated blood.
Right Atrium to Right Ventricle to Pulmonary Artery
• Deoxygenated blood from the superior vena cava enters
the right atrium, then the right ventricle, and is pumped
into the pulmonary artery.
• Since the lungs are non-functional and have high
resistance, only a small portion goes to the lungs.

Pulmonary Artery to Aorta – Ductus Arteriosus

• Most of the blood in the pulmonary artery bypasses the
lungs via the ductus arteriosus, entering the descending
aorta.

Aorta to Umbilical Arteries

• Blood flows down the aorta, delivering nutrients and
collecting waste from fetal tissues.
 TRANSITION AT BIRTH
Events:
• First breath → lungs expand → pulmonary
resistance drops.
• Increased pulmonary blood flow → left atrial
pressure rises.
• Foramen ovale closes functionally within minutes.
• Ductus arteriosus constricts due to ↑ O₂ and ↓
prostaglandins.
• Ductus venosus closes as umbilical circulation stops.