biology

1. Fertilization, Pregnancy and
Lactation
Department of Physiology
Faculty of Medicine Diponegoro
University

2. From Egg to Embryo
 Pregnancy – events that occur from fertilization
until the infant is born
 Conceptus – the developing offspring
 Gestation period – from the last menstrual
period until birth
 Preembryo – conceptus from fertilization until it
is two weeks old
 Embryo – conceptus during the third through
the eighth week
 Fetus – conceptus from the ninth week through
birth

3. Relative Size of Human
Conceptus

4. Accomplishing Fertilization
 The oocyte is viable for 12 to 24 hours
 Sperm is viable 24 to 72 hours
 For fertilization to occur, coitus must
occur no more than:
◦ Three days before ovulation
◦ 24 hours after ovulation
 Fertilization – when a sperm fuses
with an egg to form a zygote

5. Sperm Transport and
Capacitacion
 Fates of ejaculated sperm
◦ Leak out of the vagina immediately after
deposition
◦ Destroyed by the acidic vaginal
environment
◦ Fail to make it through the cervix
◦ Dispersed in the uterine cavity or
destroyed by phagocytic leukocytes
◦ Reach the uterine tubes
 Sperm must undergo capacitation
before they can penetrate the oocyte

6. Their mobility is enhanced and their membranes
must become fragile so that the hydrolytic enzymes
in their acrosomes can be released.
As sperm swim through the cervical mucus, uterus,
and uterine tubes, secretions of the female tract
cause some of their membrane proteins to be
removed, and the cholesterol that keeps their
acrosomal membranes “tough” and stable is
depleted.
They must “wait around” for capacitation to occur.
This is an elaborate mechanism for preventing the
spilling of acrosomal enzymes. But consider the
alternative—fragile acrosomal membranes in the
male reproductive tract could rupture prematurely,
causing some degree of autolysis (self-digestion)
of the male reproductive system.

7.  How sperm navigate to find a released
oocyte in the uterine tube is an area of
active research. It now appears that
they “sniff” their way to the oocyte.
Sperm are known to bear proteins
called olfactory receptors that respond
to chemical stimuli (alurin) and it is
presumed that the oocyte or its
surrounding cells release signaling
molecules that direct the sperm.

8. Acrosomal Reaction and Sperm
Penetration
 An ovulated oocyte is encapsulated by:
◦ The corona radiata and zona pellucida
◦ Extracellular matrix
 Sperm binds to the zona pellucida and undergoes the
acrosomal reaction
◦ Enzymes are released near the oocyte
◦ Hundreds of acrosomes release their enzymes to digest the
zona pellucida
 Once a sperm makes contact with the oocyte’s
membrane:
◦ Beta protein finds and binds to receptors on the oocyte
membrane
◦ Alpha protein causes it to insert into the membrane

9. Acrosomal Reaction and Sperm
Penetration

11. Blocks to Polyspermy
 Only one sperm is allowed to
penetrate the oocyte
 Two mechanisms ensure monospermy
◦ Fast block to polyspermy – membrane
depolarization prevents sperm from fusing
with the oocyte membrane
◦ Slow block to polyspermy – zonal
inhibiting proteins (ZIPs):
 Destroy sperm receptors
 Cause sperm already bound to receptors to
detach

12. Completion of Meiosis II and
Fertilization
 Upon entry of sperm, the secondary
oocyte:
◦ Completes meiosis II
◦ Casts out the second polar body
 The ovum nucleus swells, and the two
nuclei approach each other
 When fully swollen, the two nuclei are
called pronuclei
 Fertilization – when the pronuclei
come together

13. Events Immediately Following Sperm
Penetration

14.  The first cleavage produces two daughter cells
called blastomeres
 Morula – the 16 or more cell stage (72 hours
old)
 By the fourth or fifth day the preembryo
consists of 100 or so cells (blastocyst)
 Blastocyst – a fluid-filled hollow sphere
composed of:
◦ A single layer of trophoblasts
◦ An inner cell mass
 Trophoblasts take part in placenta formation
Preembryonic Development

15. Cleavage: From Zygote to
Blastocyst

16. Implantation
 Begins six to seven days after ovulation when
the trophoblasts adhere to a properly prepared
endometrium
 The trophoblasts then proliferate and form two
distinct layers
◦ Cytotrophoblast – cells of the inner layer that retain
their cell boundaries
◦ Syncytiotrophoblast – cells in the outer layer that lose
their plasma membranes and invade the endometrium
 The implanted blastocyst is covered over by
endometrial cells
 Implantation is completed by the fourteenth day
after ovulation

17. Implantation of the Blastocyst

18. Implantation
 Viability of the corpus luteum is
maintained by human chorionic
gonadotropin (hCG) secreted by the
trophoblasts
 hCG prompts the corpus luteum to
continue to secrete progesterone and
estrogen
 Chorion – developed from trophoblasts
after implantation, continues this
hormonal stimulus
 Between the second and third month, the
placenta:
◦ Assumes the role of progesterone and
estrogen production
◦ Is providing nutrients and removing wastes

19. Hormonal Changes During
Pregnancy

20. Placentation
 Formation of the placenta from:
◦ Embryonic trophoblastic tissues
◦ Maternal endometrial tissues
 The chorion develops fingerlike villi, which:
◦ Become vascularized
◦ Extend to the embryo as umbilical arteries and
veins
◦ Lie immersed in maternal blood
 Decidua basalis – part of the endometrium
that lies between the chorionic villi and the

21. Placentation
 Decidua capsularis – part of the endometrium
surrounding the uterine cavity face of the implanted
embryo
 The placenta is fully formed and functional by the
end of the third month
 Embryonic placental barriers include:
◦ The chorionic villi
◦ The endothelium of embryonic capillaries
 The placenta also secretes other hormones –
human placental lactogen, human chorionic
thyrotropin, and relaxin

22. Placentation

23. Placentation

24. Placentation

25. Hormon Plasenta

26.  Chadwick’s sign – the vagina develops a
purplish hue
 Breasts enlarge and their areolae darken
 The uterus expands, occupying most of the
abdominal cavity
 Lordosis is common due to the change of the
body’s center of gravity
 Relaxin causes pelvic ligaments and the pubic
symphysis to relax
 Typical weight gain is about 29 pounds
Effects of Pregnancy: Anatomical
Changes

27. Relative Uterus Size During
Pregnancy

28.  The placenta secretes human placental
lactogen (hPL), also called human chorionic
somatomammotropin (hCS), which stimulates
the maturation of the breasts
 hPL promotes growth of the fetus and exerts a
maternal glucose-sparing effect
 Human chorionic thyrotropin (hCT) increases
maternal metabolism
 Parathyroid hormone levels are high, ensuring a
positive calcium balance
 The average weight gain: 11 to 16 kg
Effects of Pregnancy: Metabolic
Changes

29.  GI tract – morning sickness occurs due to elevated
levels of hCG
 Urinary system – urine production increases to handle
the additional fetal wastes
 Respiratory system – edematous and nasal congestion
may occur
◦ The growing uterus presses upward against the diaphragm
 the total excursion of the diaphragm is decreased  the
respiratory rate is increased to maintain the extra
ventilation.
◦ Dyspnea (difficult breathing) may develop late in pregnancy
 Cardiovascular system – blood volume increases 25-
40%
◦ 625 mL/min of blood flows through the maternal circulation
of the placenta during the last month of pregnancy.
Effects of Pregnancy: Physiological
Changes

30. Nutrition During Pregnancy
 A number of maternal deficiencies can occur,
especially in calcium, phosphates, iron, and the
vitamins
 Without sufficient iron in her food, hypochromic
anemia may develop
 Vitamin D is essential to assist calcium
absorption.
 Vitamin K is important so that the baby will
have sufficient prothrombin to prevent
hemorrhage, particularly brain hemorrhage,
caused by the birth process.

31.  Persalinan memerlukan :
1. Dilatasi kanalis servikalis
2. kontraksi miometrium yang cukup kuat
 Weak Braxton Hicks contractions may take
place
 As birth nears, oxytocin and prostaglandins
cause uterine contractions
 Emotional and physical stress:
◦ Activates the hypothalamus
◦ Sets up a positive feedback mechanism,
releasing more oxytocin
Pelunakan/pematangan serviks oleh relaksin
Parturition: Initiation of Labor

32. Parturition: Initiation of Labor

34. Feedback Positive
Mechanism
 Oksitosin dan Prostaglandin meningkatkan kontraksi
miometrium.
 Kontraksi dimulai dari puncak uterus dan menyapu ke
bawah mendorong janin menuju serviks
 Tekanan janin thd serviks menyebabkan :
1. Kepala mendorong serviks, kanalis servikalis membuka
2. Peregangan serviks merangsang pelepasan oksitosin
mell refleks neuroendokrin
• Oksitosin menybbkan kontraksi lebih kuat
• Oksitosin merangsang Prostaglandin
• Dst sampai janin lahir

35.  From the onset of labor until
the cervix is fully dilated (10
cm)
 Initial contractions are 15–30
minutes apart and 10–30
seconds in duration
 The cervix effaces and dilates
 The amnion ruptures,
releasing amniotic fluid
(breaking of the water)
 Engagement occurs as the
infant’s head enters the true
Stages of Labor: Dilation
Stage

36.  From full dilation to
delivery of the infant
 Strong contractions occur
every 2–3 minutes and
last about 1 minute
 The urge to push
increases in labor without
local anesthesia
 Crowning occurs when
the largest dimension of
the head is distending the
Stages of Labor: Expulsion
Stage

37.  The delivery of the placenta is accomplished
within 30 minutes of birth
 Afterbirth – the placenta and its attached fetal
membranes
 All placenta fragments must be removed to
prevent postpartum bleeding
Stages of Labor: Expulsion
Stage

38.  At 1-5 minutes after birth, the infant’s
physical status is assessed based on
five signs: heart rate, respiration,
color, muscle tone, and reflexes
 Each observation is given a score of 0
to 2
 Apgar score – the total score of the
above assessments
◦ 8-10 indicates a healthy baby
◦ Lower scores reveal problems
Extrauterine Life

39. First Breath
 Once carbon dioxide is no longer removed
by the placenta, central acidosis occurs
 This excites the respiratory centers to
trigger the first inspiration
 This requires tremendous effort – airways
are tiny and the lungs are collapsed
 Once the lungs inflate, surfactant in alveolar
fluid helps reduce surface tension

40.  Umbilical arteries and vein constrict and
become fibrosed
 Fates of fetal vessels
◦ Proximal umbilical arteries become superior
vesical arteries and distal parts become the
medial umbilical ligaments
◦ The umbilical vein becomes the ligamentum
teres
◦ The ductus venosus becomes the ligamentum
venosum
◦ The foramen ovale becomes the fossa ovalis
◦ The ductus arteriosus becomes the ligamentum
Occlusion of Fetal Blood
Vessels

41. Transitional Period
 Unstable period lasting 6-8 hours after birth
 The first 30 minutes the baby is alert and
active
◦ Heart rate increases (120-160 beats/min.)
◦ Respiration is rapid and irregular
◦ Temperature falls
 Activity then diminishes and the infant sleeps
about three hours
 A second active stage follows in which the
baby regurgitates mucus and debris
 After this, the infant sleeps, with waking

42.  The production of milk by the
mammary glands
 Estrogens, progesterone, and
lactogen stimulate the hypothalamus
to release prolactin-releasing hormone
(PRH)
 The anterior pituitary responds by
releasing prolactin
Lactation

43. Breasts
Development
 At puberty: The breasts
begin to develop stimulated
by the estrogens by
stimulation of the breasts'
mammary glands plus the
deposition of fat to give the
breasts mass.
 At the high-estrogen state
of pregnancy: the glandular
tissue become completely
developed for the production
of milk.

44. The Role of Estrogen and
Progesterone
in Breasts Growth
 Estrogens are secreted by the placenta cause
the ductal system of the breasts to grow and
branch, the stroma of the breasts increases in
quantity, and large quantities of fat are laid
down in the stroma.
 Other important hormones: growth hormone,
prolactin, the adrenal glucocorticoids, and
insulin.
 Final development of the breasts into milk-
secreting organs also requires progesterone.
 Progesterone causes additional growth of the
breast lobules, with budding of alveoli and

45. Prolactin Promotes Lactation
 Although estrogen and progesterone are essential for
the physical development of the breasts during
pregnancy, a specific effect of both these hormones is
to inhibit the actual secretion of milk (menghambat
efek prolaktin)
 Conversely, the hormone prolactin has exactly the
opposite effect on milk secretion-promoting it. This
hormone is secreted by the mother's anterior pituitary
gland, and its concentration in her blood rises steadily
from the fifth week of pregnancy until birth of the
baby, at which time it has risen to 10 to 20 times the
normal nonpregnant level.
 The placenta secretes large quantities of human
chorionic somatomammotropin, which probably has
lactogenic properties, thus supporting the prolactin
from the mother's pituitary during pregnancy.

46. Ejection (or "Let-Down") Process in
Milk Secretion-Function of Oxytocin
 Milk is secreted continuously into the alveoli of
the breasts, but it does not flow easily from the
alveoli into the ductal system and, therefore,
does not continually leak from the breast
nipples. Instead, the milk must be ejected from
the alveoli into the ducts before the baby can
obtain it. This is caused by a combined
neurogenic and hormonal reflex that involves
the posterior pituitary hormone oxytocin, as
follows.

47.  When the baby suckles, it receives virtually no milk
for the first half minute or so. Sensory impulses
must first be transmitted through somatic nerves
from the nipples to the mother's spinal cord and
then to her hypothalamus, where they cause nerve
signals that promote oxytocin secretion at the same
time that they cause prolactin secretion. The
oxytocin is carried in the blood to the breasts,
where it causes myoepithelial cells (which surround
the outer walls of the alveoli) to contract, thereby
expressing the milk from the alveoli into the ducts.
Then the baby's suckling becomes effective in
removing the milk. Thus, within 30 seconds to 1
minute after a baby begins to suckle, milk begins to
flow. This process is called milk ejection or milk
let-down.

48.  Suckling on one breast causes milk
flow not only in that breast but also in
the opposite breast.
 Fondling of the baby by the mother or
hearing the baby crying often gives
enough of an emotional signal to the
hypothalamus to cause milk ejection.
 Many psychogenic factors or even
generalized sympathetic nervous
system stimulation throughout the
mother's body can inhibit oxytocin
secretion and consequently depress
milk ejection.

49.  Immediately after the baby is born, the sudden loss of
both estrogen and progesterone secretion from the
placenta allows the lactogenic effect of prolactin from
the mother's pituitary gland to assume its natural milk-
promoting role, and over the next 1 to 7 days, the
breasts begin to secrete copious quantities of milk
instead of colostrum.
 This secretion of milk requires an adequate background
secretion of most of the mother's other hormones as
well, but most important are growth hormone, cortisol,
parathyroid hormone, and insulin. These hormones are
necessary to provide the amino acids, fatty acids,
glucose, and calcium required for milk formation.
 After birth of the baby, the basal level of prolactin
secretion returns to the nonpregnant level over the next
few weeks. However, each time the mother nurses her
baby, nervous signals from the nipples to the
hypothalamus cause a 10- to 20-fold surge in prolactin

51.  This prolactin acts on the mother's breasts
to keep the mammary glands secreting milk
into the alveoli for the subsequent nursing
periods.
 If this prolactin surge is absent or blocked
as a result of hypothalamic or pituitary
damage or if nursing does not continue, the
breasts lose their ability to produce milk
within 1 week or so.
 However, milk production can continue for
several years if the child continues to
suckle, although the rate of milk formation
normally decreases considerably after 7 to

52. Hypothalamus Secretes Prolactin
Inhibitory Hormone
 The hypothalamus plays an essential role in controlling
prolactin secretion. However, this control is different in
one aspect: The hypothalamus mainly stimulates
production of all the other hormones, but it mainly
inhibits prolactin production. Consequently, damage to
the hypothalamus or blockage of the hypothalamic-
hypophysial portal system often increases prolactin
secretion while it depresses secretion of the other
anterior pituitary hormones.
 Therefore, it is believed that anterior pituitary secretion
of prolactin is controlled either entirely or almost entirely
by an inhibitory factor formed in the hypothalamus and
transported through the hypothalamic-hypophysial
portal system to the anterior pituitary gland. This factor
is called prolactin inhibitory hormone. It is almost
certainly the same as the catecholamine dopamine,
which is known to be secreted by the arcuate nuclei of
the hypothalamus and can decrease prolactin secretion
as much as 10-fold.

53. Lactation
 Colostrum
◦ The fluid secreted during the last few days
before and the first few days after
parturition Solution rich in vitamin A,
protein, minerals, and IgA antibodies
◦ Is released the first 2–3 days
◦ it has almost no fat
◦ Is followed by true milk production

54.  After birth, milk
production is
stimulated by
the sucking
infant
Lactation and Milk Let-down
Reflex

55. Breast Milk
 Advantages of breast milk for the infant
◦ Fats and iron are better absorbed
◦ Its amino acids are metabolized more efficiently
than those of cow’s milk
◦ Beneficial chemicals are present – IgA, other
immunoglobulins, complement, lysozyme,
interferon, and lactoperoxidase. Also, several
different types of white blood cells are secreted,
including both neutrophils and macrophages.
◦ Interleukins and prostaglandins are present, which
prevent overzealous inflammatory responses
◦ Its natural laxatives help cleanse the bowels of
meconium

56. Advantages of breast milk for the
mother
 Mempercepat involusi uterus (pelepasan
oksitosin)
 Dapat menekan siklus haid dengan
menghambat LH dan FSH, menghambat
GnRH (metode kontrasepsi)

57. Metabolic Drain on the Mother
Caused by Lactation
 About 1.5 liters of milk may be formed each day
(maybe more for twins).
 So great quantities of energy are drained from the
mother; approximately 650 to 750 kCal/L are
contained in breast milk
 The output of calcium and phosphate in breast milk >
the intake of these substances. The parathyroid
glands hence enlarge and the bones become
decalcified.
 The mother's bone decalcification becomes more
important during lactation.