BMSN2202 - Life Science II

(Physiology & Biochemistry)

Pregnancy and Lactation

Calvin KF Lee
L7-49, Laboratory Bock, FOMB
Obstetrics and Gynaecology
Email: ckflee@hku.hk
Outline
1. Define the process of embryo Implantation and
Pregnancy
2. List the functions of placenta
3. List the placental hormones and their functions
during pregnancy
4. Describe the physiological changes in
pregnancy
5. Define three parturition stages
6. Describe the mechanism of Lactation
 1. Embryogenesis

Egg

8 wk human embryo
4-cells

8-cells
Blastocyst
Morula
1. Implantation on LH+7 day
1. Embryo Implantation
1. Pregnancy
Childbirth usually occurs about 38 weeks
after conception
280 days (40 weeks) after last menstruation
period (LMP), or
266 days: (38 weeks) after fertilization
1. Pregnancy
The first trimester: highest risk of miscarriage
In the second trimester: the development of the fetus can
be more easily monitored and diagnosed
The beginning of the third trimester: often approximates
the point of viability, or the ability of the fetus to survive
outside of the uterus
2. Placenta
The outer layer of the
blastocyst (trophoblast),
forms the outer layer of the
placenta
Sub-divided into two further
layers:
Cytotrophoblast layer, and
Syncytiotrophoblast layer
2. Placenta
The syncytiotrophoblast is
a multinucleated
continuous cell layer that
covers the surface of the
placenta
It forms as a result of
differentiation and fusion of
the underlying
cytotrophoblast cells, a
process that continues
throughout placental
development
2. Function of the placenta
Respiratory gas exchange: Concurrent
passive diffusion, with area, permeability
and blood flows
Glucose: facilitated diffusion with Glut
transporters
Calcium: Active cation transport; other
amino acids via coupled sodium transport
Immunoglobulins (IgG): endocytosis
2. Chorionic Gonadotrophin
Secreted from 8-cell embryos
60
& syncytiotrophoblast
Stimulated by GnRH from 50

cytotrophoblast 40
Rescue the corpus luteum
30
Stimulates fetal gonads to
produce steroid hormones 20

Used for pregnancy test 10

0
0 4 8 12 16 20 24 28 32 36 40
Duration of
Textbook ofpregnancy
Medical Physiology (Ed. A.C. Guyton)
2. Human placental lactogen
Protein hormone from placenta (hPL/hCS), with
placental mass
Structurally related to PRL & GH (96%)
Lactogenic activity in human?
Functions in fat & carbohydrate metabolism
Inhibit peripheral glucose uptake;
Increase plasma free fatty acids
A steady supply of glucose to fetus
2. Other placental hormones
Placental growth hormone (PGH): regulating fetal
growth
Corticotropin-releasing hormone (CRH) & Pro-
opiomelanocortin (POM-C), precursor of
adreocorticotropic hormone (ACTH) rise in the
last month of pregnancy
Timing of the onset of parturition?
3. Estrogens
Syncytiotrophoblast
From maternal adrenal 24
androgen 20
Mainly estriol (weak) but large
amount 16
Enlargement of uterus, female
external genitalia 12

Growth of breast ductal 8

structure
Relaxation and softening of 4
pelvic ligaments and pubis
symphysis (with relaxin) 0
0 4 8 12 16 20 24 28 32 36 40
Duration of
pregnancy
Textbook of Medical Physiology (Ed. A.C. Guyton)
3. Progesterone
Syncytiotrophoblast
oviductal & uterine secretion
decidual cell development
30
Maintains pregnancy 0

contractility of uterus
200
sensitivity to oxytocin
prostaglandin production 10
immune response to fetus 0

Stimulate endometrial
0
vascularization 0 4 8 12 16 20 24 28 32 36 40

Prepare breasts for lactation Duration of

pregnancy
Textbook of Medical Physiology (Ed. A.C. Guyton)
 3. Hormones (E & P) synthesis
Mother Placenta Fetus
(Cannot synthesize (Deficiency in
cholesterol) 3b-OH dehydrogenase)
Adrenal DS, Adrenal DS,
DS
DHEA (TA) DHEA (TA)
Sulfatase
Cholesterol Cholesterol
DHEA (AT)
Estrogen pool
- Bound to SHBG Aromatase
- uterine blood flow
E1 E2
- uterine contractility Target
Progesterone pool Progesterone tissues
- Bound to CBG
- Modulates blood flow
- Inhibits uterine contractility
4. Embryonic period
4th to 8th week
Establishment of 3 germ layers
Ectoderm: skin, neuron

Mesoderm: muscle and blood

Endoderm: GI tract, glands

4. Development of human embryo
4. Embryonic period
Pharyngeal
arches

Heart
bulge
Ear
Eye

Somites
Toe
4th week 7th-8th week
Langmans Medical Embryology (Ed T.W. Sadler)
4. Ultrasound Scan ()

7 wk

13 wk

9 wk
4D ultrasound - Fetus at 13 weeks
-
Langmans Medical Embryology (Ed T.W. Sadler)
4. Growth of Fetus
Length
12 wk: 10 cm
20 wk: 25 cm
40 wk: 53 cm

Weight
23 wk: 1 pound
32 wk: 3 pound
36 wk: 4.5 pound
40 wk: 7 pound
5. Physiological changes
Maternal adaptation to pregnancy
Volume support: Volume expansion, vasodilatation
Nutrition: respiration, peripheral insulin resistance,
mineral absorption
Waste clearance: renal glomerular filtration,
hepatocellular stimulation
Pregnancy maintenance/maturation: Uterine
quiescence, immunological sequestration
Normal pregnancy weight gain = 11.315.9 kg
(2535 pounds)
5. Maternal changes
Cardiovascular system: >40% blood volume
Respiratory system: tidal volume
Kidney and urinary tract: GFR & RPF
Gastrointestinal tract & metabolism: hyperinsulinism
()
hPL promote lipolysis and release of fatty acids that cause
insulin resistance
Ensure a continuous supply of glucose to fetus
Haematological system: Mildly anaemic (vol )
 5. Summary
Anabolic phase
sensitivity to insulin
lipogenesis, lipolysis
protein synthesis
growth of breast, uterus and
essential musculature for
pregnancy and labor
glycogen store in liver and
muscle
Plasma levels of glucose, AA
and fatty acids normal or low
Catabolic phase
insulin resistant (placental
HCS)
Lipogenesis, protein
synthesis and glycogenesis
lipolysis
Plasma levels of glucose,
AA and fatty acids
Nutrients siphoned to the
fetus
6. Initiation of labour
Mechanism not completely known
Multiple mechanisms involving maternal and
fetal components
High redundancy (one can replace the others)
No single trigger: Once triggered positive
feedback of a cascade of events parturition
6. Initiation of labour
Increase in aromatase
activity -> E2 level 2
4
maternal oxytocin -> 2
0 300
control time of day that 16

labour will start 12 200

Use clinically to induce 8 10

labour 0
4
synthesis & release of 0
0
0 4 8 12 16 20 24 28 32 36 40
prostaglandins -> uterine Duration of
contraction Textbookpregnancy
of Medical Physiology (Ed. A.C. Guyton)
6. Relaxin
Facilitate parturition
First from corpus luteum, then from placenta
Stimulated by hCG
Function:
1. Relaxation of pelvic ligament
2. Dilation of cervix
3. Suppression of uterine contraction (in early
pregnancy)
 HYPOTHALAMUS

6. Oxytocin
From hypothalamus
POSTERIOR
Released from posterior PITUITARY
pituitary
Stimulated by tactile BRAINSTEM
Oxytocin
stimulation of
reproductive tract,
particularly cervix
Enhanced by high
estrogen : progesterone
ratio
Increase prostaglandin
production/release
Modified from Essential Reproduction (Eds M. Johnson & B. Everitt)
6. Fetal factor
Hormonal factor
Oxytocin (fetal pituitary gland)
Cortisol (fetal adrenal gland)
Prostaglandin (Fetal amniotic and chorionic
membrane)

Mechanical stretch of the uterine

musculature
6. Parturition
Process by which the baby is born
Expulsion of the baby involved
Rhythmic contraction of uterus
Ripening of the cervix -> softer and
easily dilatable
6. 1st stage of labour
Dilation stage
Begins with regular uterine contractions from
fundus
widening of cervix
Ends with full dilation of cervix
Duration
1st pregnancy: 10-12 hrs (primigravidas),
2nd pregnancy: 6-8 hrs (multigravidas)
6. 2nd stage of labour
Expulsion stage
Begins with fully dilated cervix
Ends when the fetus is forced out of uterus
through the cervix by contraction of
uterine muscle
voluntary muscles of the abdominal wall and
diaphragm
Duration
1st pregnancy: 1 hr (primigravidas),
2nd pregnancy: 15-30 mins (multigravidas)
6. Contraction of the uterus
Intensity of contraction

Minutes

Contraction: downward at 2cm/sec

6. 3rd stage of labour
Placental stage
Begins from the birth of the child
Ends with
separation of placenta from decidua tissues of
uterus
expulsion of placenta and membranes
Myometrial contractions
constriction of blood vessels
prevent excessive bleeding
Duration : 10 min
 Non-pregnant Pregnant Lactating

7. Breast
Each breast contains 1525 lobes
Each lobe contains many lobules
Milk is produced in Sacs
Hormonal stimulation

1. Chest wall
2. Pectoralis muscles
3. Lobules
4. Nipple
5. Areola
6. Milk duct
7. Fatty tissue
8. Skin
7. Hormones on breast
development & Lactation
Ductal growth
Estrogen, Growth hormone (GH), Adrenal steroids
Lobulo-alveolar growth
Estrogen, Progesterone, prolactin, GH, adrenal
steroids
Milk secretion
Prolactin (stimulate synthesis b-lactoglobulin & casein
in breast tissue, stimulate milk fat), adrenal steroids,
insulin
7. Colostrum
A form of milk produced by the mammary glands
of mammals (including humans) in late pregnancy
Contains immune cells (as lymphocytes)
antibodies (IgA, IgG, and IgM) to protect the
newborn against disease
Lower in fat and higher in protein than ordinary
milk
Mild laxative effect - encourage the passing of the
baby's first stool (excrete excessive bilirubin)
7. Hormones in lactation
PREGNANCY LACTATION
Conception Birth Weaning

Estrogen at basal
until cycle begin

Mature milk
Transitional milk
Milk secretion Colostrum
1 2 3
Weeks post-partum
7. Milk ejection or letdown
Suckling stimulus (Oxytocin releases from
posterior pituitary, causes contraction of
myoepithelial cells of the milk ducts)
Crying or sight of an infant
Inhibited by pain, embarrassment or alcohol
Sucking reflex affects GnRH pulse generator:
Inhibits gonadotropin release and ovulation may
not occur.
 7. Neuroendocrine control of
lactation
HYPOTHALAMUS HYPOTHALAMUS
Dopamine
(PIF)

Portal vessel
POSTERIOR
PITUITARY

ANTERIOR BRAINSTEM BRAINSTEM

PITUITARY Oxytocin
Prolactin
Alveolar cells Myoepithelial cells
(milk production) (milk ejection)

Nipple suckling Nipple suckling

References
1. Textbook of Medical Physiology (A.C. Guyton & J.E. Hall)
2. Physiology (R.M. Berne and M.N. Levy)
3. Essential Reproduction (M.H. Johnson and B.J. Everitt)
4. Langmans Medical Embryology (T.W. Sadler)
5. Functional Histology. A Text and Colour Atlas (PR
Wheater, H.G. Burkitt, V.G. Daniels) 2nd edition, ELBS
6. The Reproductive System at a Glance (L.J. Heffner &
J.D. Schust) 2nd edition, Blackwell publishing