Physiology of Pregnancy 050918

Physiology of Pregnancy,
Parturition and Lactation
Indri Ngesti Rahayu, dr., M.Kes.

Department of Physiology
Medical Faculty Universitas Hang Tuah Surabaya
Reproduction Block Physiology Lecture 5th semester Wednesday, September 05, 2018 1
Pregnancy
1. Fertilization
2. Placenta development, nutrition
3. Hormonal changes during
pregnancy
4. Other physiological changes
5. Metabolism
6. Parturition (Labor)
7. Lactation and breastfeeding
Fertilization
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:
o Three days before ovulation
o 24 hours after ovulation
• Sperm can reach the ampulla within 10-
20 minutes of coitus
Acrosomal Reaction and
Sperm Penetration
• An ovulated oocyte is encapsulated by:
o The corona radiata and zona pellucida
• Sperm binds to the zona pellucida and
undergoes the acrosomal reaction
o Enzymes are released near the oocyte
o Hundreds of acrosomes release their
enzymes to digest the zona pellucida
Blocks to Polyspermy
• Only one sperm is allowed to penetrate
the oocyte
• Two mechanisms ensure monospermy
o Fast block to polyspermy – membrane
depolarization prevents sperm from fusing
with the oocyte membrane
o Slow block to polyspermy – zonal inhibiting
proteins (ZIPs):
• Destroy sperm receptors
• Cause sperm already bound to receptors
to detach
Acrosomal Reaction and Sperm Penetration
Union of Male & Female Chromosomes
• Sperm capacitation
• Sperm motility and
vaginal, cervical,
uterine, and oviduct
contractions
• Egg contact
• Penetration
• Nuclear fusion
• (Zygote)
Fertilization
Fertilization in
the ampulle of
the FT.
• Prostaglandins
• Oxytocin
Ectopic (extrauterine)
gravidity
Fertilization
Transport into
the uterus - 3-5
days
• Contraction of
the FT isthmus
• Relaxation -
progesteron
Fertilization
Implantation 5-7
days after
fertilization
• Proteolytic
enzymes of the
trophoblast cells
Implantation of the Blastocyst
Transfer of Fertilized Ovum
• 3-5 days after fertilization, fertilized ovum
(blastocyst) is transported to the uterus
• This is aided by fluid current in the tube,
action of the ciliated epithelium, and
possibly contractions of the fallopian
tube
• Blastocyst with about 100 cells reaches
the uterus
Implantation of the Blastocyst
• After reaching uterus, blastocyst stays another

1-3 days before implantation
• Blastocyst gets nutrition from uterine milk
• Trophoblast cells secrete enzymes that digest
the adjacent cells of endometrium
• After implantation, trophoblast cells and other
adjacent cells proliferate rapidly to form
placenta and other membranes of pregnancy
Cell Division & Implantation
Embryonic Development
• In early gestation Embryo is nourished
by secretions of the oviduct and uterine
endometrial glands
• Uterine secretions include growth
factors (e.g. TNFa, epidermal growth
factor) that promote placental growth
• Growth trajectories of both placenta and
fetus are established early & have
lifelong consequences
Nutrient Availability & Maternal
Metabolic Status
• Blastocyst development & implantation are
reduced
o diabetic mothers
o animal models with insufficient nutrients
• Poorly nourished women and obese
women at risk for aberrations in embryonic
and placental development
o Congenital anomalies
o Adverse outcomes later in pregnancy (e.g.
preeclampsia)
Placenta
Placenta
• The major function of placenta is to provide diffusion of

gases, foodstuffs, and waste
• Placenta starts providing nutrition after the 16th day
after fertilization
The Placenta
• 10-12 weeks is the period of placentation
• Rapid early growth prepares way for fetal
growth
• Trophoblast cells use same molecular
mechanisms as tumors, but are highly
regulated and controlled
Placental Functions
• Maintains immunological distance
between mother and fetus
• Special endocrine organ: “transient
hypothalamo-pituitary-gonadal axis”
• Responsible for exchange of nutrients,
gases & metabolic waste products
between maternal and fetal circulation
Placental Architecture
• Maternal and fetal blood do not mix:
“placental barrier”
o Fetal blood flows through capillary
networks within highly branched
terminal chorionic villi
o Maternal blood flows through intervillous
space
• Uterine arteriols bring blood in
• Uterine venules drain blood
Placenta works as a
physiological A-V shunt
Placenta development
• Early nutrition of the embryo - invasion of trophoblastic cells
into the decidua
• Progesteron produced by CL - stimulates decidual cells to
concentrate glycogen, proteins and lipids
Placenta - oxygen transport
•Similarities betwen placenta and lungs
•Oxygen transport - simple difusion
Lungs
• pO2 in alveoli…………………………..100mmHg
• pO2 in the venous blood……………40mmHg
• dO2 in (pressure gradient)…………60mmHg
Placenta:
• pO2 in placental sinuses…………50mmHg
• pO2 in fetal umbilical vein………30mmHg
• dO2 in (pressure gradient)………20mmHg
How is a sufficient oxygenation of the fetus possible?

Placenta - oxygen transport
1. Fetal hemoglobin
2. Higher Hb concentration in
the fetal blood
(50% more than in adults)
3. Double Bohr effect

- Hb can carry more oxygen in
low pCO2 than in high pCO2
Placenta - CO2, nutritients,
waste products transport
• CO2 gradient - 2-3 mmHg, but extreme solubility
(diffuses 20times faster than oxygen)
• facilitated diffusion for glucose
(high glucose need in 3dr trimester)
• free diffusion of fatty acids
• diffusion of waste products based on concentration gradient
• drugs crossing placental barier - teratogens:

• Talidomide, Carbamazepine, Coumarins, Tetracycline…
• Alcohol, nicotine, heroin, cocaine, caffeine
• drugs (excluding alcohol) - 3% of all congenital
malformations
Placenta and Further Embryonic Development
Diffusion of O2 and CO2
• The same process as pulmonary
membranes
• Simple diffusion
• Fetal hemoglobin has more affinity
to O2
• Fetal hemoglobin (Hb)
concentration is 50% higher than
maternal Hb
Foodstuff and waste
products Diffusion
• Simple and facilitated diffusion
Maternal to Infant Nutrient Transportation
Across The Placenta
Substance Primary Mechanism
Water, electrolytes, urea, free fatty Passive diffusion

acids, steroids, fat soluble vitamins
Glucose Facilitated diffusion
Amino acids, water soluble Active transport

vitamins, calcium, iron, iodine
Globulins, phospholipids, Pinocytosis and endocytosis
lipoproteins
Water, electrolytes Bulk flow (due to changes in
hydrostatic or osmotic forces),
solvent drag
Psychology of Pregnancy
• Psychosocial adaptation
o Process over time
o Prerequisite for developing parental identify
and behavior
• Factors that impact psychosocial
adaptation
o Pregnancy intendedness
o Stress & depression
Why do we care in terms of
nutrition?
• Stress interferes with ability to

achieve developmental tasks
• Developmental tasks key to ability of
mother to take care of herself and her
baby nutritionally.
Hormonal Changes
During Pregnancy
Hormonal Factors in Pregnancy
• Placenta forms large quantities of: 1.

human chorionic gonadotropin
(hCG), 2. estrogen, 3. progesterone,
4. human chorionic
somatomammotropin
Human Chorionic
Gonadotropin (hCG)
• Secreted by trophoblast 8-9 days after ovulation
• Responsible for “maternal recognition of
pregnancy”
• The same structure and function of LH
• Maintains corpus luteum (CL)
• Promotes estrogen and progesterone secretion
from CL (CL is important in the first 3 months)
• Stimulates testosterone production by the testes
of male fetus (development and decent of
testes)
Human Chorionic
Somatomammotropin
• Prolactin like effect (human palcental

lactogen)
• Decreases maternal insulin sensitivity and
enhances fat mobilization (making more
glucose available to the fetus)
Hormonal changes
Human Chorionic Gonadotropin
HCG • prevent involution of CL
(pregesterone, estrogen)
•effect on the testes of male
fetus - development of sex
organs
Human Chorionic
Somatomammotropin
HCS • effect on latation (HPL) ?
•growth hormone effects
•decreases insulin sensitivity -
more glucose for the fetus
• low levels - placental insuf.
Estrogen from Placenta
• Placental estrogen levels are 30 times higher
than normal E production
• Not synthesized de novo, it is converted from
androgenic steroids from the mother and
fetus adrenal glands
• Functions of E during pregnancy include:
1. Enlargement of the uterus, 2. growth of breasts,
3. Enlargement of female external genitalia
4. Relaxes the pelvic ligaments
Progesterone From Placenta
• Placenta secrets high quantities of P
• Its functions include:
1. Development of decidual cells in the uterine
endometrium
2. Decreases the contractility of the uterus
3. Development of fetus even before
implantation by increasing the production of
nutrients by fallopian tubes and uterus
4. Acts along with estrogen to prepare mother’s
breast for lactation
Hormonal changes
Progesterone • development of decidual cells
• decreases uterus contractility
• preparation for the lactation
• enlargement of uterus
Estrogens • breasts development
• relaxation of ligments
• estriol level - indicator of

vitality of the fetus
Hormonal Changes During Pregnancy
Other hormonal factors
• Pitutary ( ACTH, TSH, prolactin)
• Corticsteroids: increased gluco- and
mineralocorticoids
• Thyroid increased
• Parathyroid increased (more calcium
available)
• relaxin
Progesterone and Cortisol metabolism
Placenta
Hormonal changes
Placenta Mother
CRH ACTH aldosterone hypertension
cortisol
edema
insulin resistance
HCG
hyperthyroidism
HC thyrotropin gestational
diabetes
Calcium demands Hyperparathyroidism
Other Physiological
Changes
Reproduction Block Physiology Wednesday, September

46
Lecture 5th semester 05, 2018
Cardiovascular changes
Cardiac output (CO)
• 30 -50% above normal
• placental circulation • ECG changes
• increased metabolism • functional murmurs
• skin - thermoregulation • heart sounds
• renal circulation
• decreases in last 8 weeks (uterus compresses vena cava)

• incr. 30% more during labor
• Heart rate (HR) increases up to 90/min

• Blood pressure (BP) drops, periferal resistance decreases
• with twins CO increases more, BP drops more

Hematologic changes
• plasma volume increases (50%)
• erythropoesis (RBC) increases (25%)
• decreased Hb, hematocrite
• Iron requirements increases significantly

• Iron suplements needed
Respiratory changes
• oxygen consumption increases

• 20% above normal
• Frequency increases
• Progesterone increases sensitivity • Minute ventilation

for CO2 in respiratory centre increases (50%)
• pCO2 decreases slightly
• Growing uterus
Urinary system
• Glomerulat filtration rate and renal plasma flow increases
(up to 30 - 50 %)
• Increased reabsorption of ions and water

- placental steroids
- aldosterone
• Slight increase of urine formation
• Postural changes affect renal functions

- upright position
- supine position
- lateral position during sleep
Preeclampsia, Eclampsia
• Preeclampsia - pregnancy induced hypertension + proteinuria
• Incresing BP since 20th week - hypertension
• Salt and water retention - edema formation
• RBF and GFR decreases
• extensive secretion of placental hormones ?

• insufficient blood supply to placenta - ischemia
- increased resistance
- TNF alfa, cytokines ?
•Eclampsia - vascular spasms, chronic seizures, coma
Emerging Understandings
• Cytokines & Inflammatory molecules are
produced by the placenta as well as adipocytes
• Adverse outcomes in obese women may be
associated with imbalances due to
overproduction from both sources
• “In pregnancy complicated with obesity or DM,
continuous adverse stimulus is associated with
dysregulation of metabolic, vasular and
inflammatory pathways.”
Nutrition and
Metabolism
Maternal weight gain
Fetus
5 kg
Mother
6 kg
Maternal-Fetal Metabolism
• 250 - 300 extra kcal/day should be ingested
- 85% fetal metabolism, 15% stored in maternal fat
• Extra protein intake - 30g/day
• End of pregnancy - fetal glucose need 5mg/kg/min
(mother 2,5mg/kg/min)
• 2 phases of pregnancy:
1st - 20th week - mother´s anabolic phase:
- anabolic metabolism of the mother
- quite small nutrition demands of the conceptus
21 - 40 week (esp. last trimester):
- high metabolic demands of the fetus
- accelerated starvation of the mother
Maternal-Fetal Metabolism
Mother´s anabolic phase:
- normal or increased sensitivity to insulin
- lower plasmatic glucose level
- lipogeneses, glycogen stores increases
- growth of breasts, uterus,weight gain
Catabolic phase (accelerated starvation):

- maternal insuln resistance
- increased transport of nutritients trough placental
membrane
- lipolysis
• Insulin resistance caused by HCS, cortisol and growth hormone

Special nutrition need in
pregnancy
• High protein diet, higher energy uptake
• Iron supplements - 300mg ferrous sulfate
• B - vitamins - erythropoesis
• Folic acid (folate) - reduces risk of neural tube defects
• Vitamin D3 + Ca supplements
• Before parturition - K vitamin (prevention of intracranial bleeding
during the labor)
Parturition
(Labor)

58
Parturition
• Means birth of the baby
• Toward the end of pregnancy, uterus becomes
progressively more excitable
• Estrogen:Progesterone ratio:- progesterone
inhibits contractility while estrogen stimulates.
• Oxytocin: increases contractions
• Fetal hormones: oxytocin, adrenal gland,
prostaglandin
• Mechanical stretch of uterine muscles
increases contractility
• Stretch of the cervix also stimulate uterine
contractions
Reproduction Block Physiology
Lecture 5th semester
Wednesday, September
05, 2018
59
Onset of labor:
• Braxton Hicks contractions: increase toward
the end of pregnancy
• Positive feedback: stretch of the cervix by fetal
head increases contractility
• Cervical stretching also cause oxytocin release
• Strong uterine contraction and pain from the
birth canal cause neurogenic reflexes from
spinal cord that induce intense abdominal
muscle contractions

60
Parturition: Initiation of Labor

61
Labor

62
The Stages of Labor

63
Lactation and
Breastfeeding

64
Breastfeeding
Infant Health Benefits
• COLOSTRUM
o Small amount for the immature
digestive system
o ‘paints’ the digestive tract
o Low fat for easy digestion
o Contains mothers antibodies which
boost infants’ immune system
o Acts as a laxative to ease passage of
meconium
65
Breastfeeding
Infant Health Benefits
• The milk comes in
o Transitional milk for up to 2 weeks
• May still have yellow appearance
• Amounts increase quickly as infant hungers and
digestive system matures
o Mother's" milk making” changes from
endocrine to autocrine system
o Mature milk
• Supply/demand system engorgement decreases
• Properties of fore milk and hind milk present
66
Lactation
Anatomy and Physiology
• Breast enlargement
o During pregnancy and lactation
indicates the mammary glands are
becoming functional
o Breast size before pregnancy does
not determine the amount of milk a
woman will produce

67
Lactation
• Hormones during pregnancy
o Estrogen stimulates the ductile
systems to grow, then estrogen levels
drop after birth
o Progesterone increases the size of
alveoli and lobes
o Prolactin contributes to increasing
the breast tissue during pregnancy
68
Lactation
• Alveoli secrete milk and contract
when stimulated
• Oxytocin stimulates milk secretion and
is released during the ‘let down’ or milk
ejection reflex
• After let down, milk travels into the
ductules, then to the larger –
lactiferous or mammary ducts

69
Lactation
• Hormones during breastfeeding
o Prolactin levels rise with nipple
stimulation
o Alveolar cells make milk in response
to prolactin when the baby sucks
o Oxytocin causes the alveoli to
squeeze the newly produced milk
into the duct system
70
Lactation: Producing and Releasing Milk
• Estrogen: growth of ductile system

• Progesterone: development of lobule-
alveolar system
• Both E and P inhibit milk production
• Prolactin stimulate milk production
o (other roles in fertility)
• Sucking stimulus 
• Oxytocin 
o "Milk let-down" reflex
71
Lactation: Producing and Releasing Milk

72
The Milk Let-Down Reflex

73
Lactation
Latch On and sucking
Oxytocin Release
Releases Milk
Infant Empties Breast
Production Increases
Milk Production Occurs
Interference with this cycle decreases the milk

Reproduction Block Physiology
supply.
Wednesday, September
74
References
• Hall JE, 2016. Guyton and Hall. Textbook of Medical
Physiology. 13th ed. Chapter 83. Pregnancy and
Lactation. Elsevier. pp 1064-1066.
• Barrett KE, Barman SM, Boitano S, Brooks HL. 2012.
Ganong’s Review of Medical Physiology. 24th ed.
Chapter 22. Reproductive Development& Function
of the Female Reproductive System, McGraw Hill,
pp. 391-418
• Sherwood, L., 2013, Human Physiology: From Cells to
Systems : Chapter 20 The Reproductive System, 8th
ed., Cengage Learning Canada, pp. 745-794
• Boron WF and Boulpaep EL. 2005. Medical
Physiology. New York : Elsevier Saunders. Chapter
55. Pp 1167-1185.
75

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Physiology of Pregnancy,

Parturition and Lactation

Indri Ngesti Rahayu, dr., M.Kes.

• After reaching uterus, blastocyst stays another

• The major function of placenta is to provide diffusion of

How is a sufficient oxygenation of the fetus possible?

3. Double Bohr effect

• drugs crossing placental barier - teratogens:

• Simple and facilitated diffusion

Water, electrolytes, urea, free fatty Passive diffusion

Amino acids, water soluble Active transport

• Stress interferes with ability to

• Placenta forms large quantities of: 1.

• Prolactin like effect (human palcental

• estriol level - indicator of

Calcium demands Hyperparathyroidism

Reproduction Block Physiology Wednesday, September

• decreases in last 8 weeks (uterus compresses vena cava)

• Heart rate (HR) increases up to 90/min

• with twins CO increases more, BP drops more

• Iron requirements increases significantly

• oxygen consumption increases

• Progesterone increases sensitivity • Minute ventilation

• Increased reabsorption of ions and water

• Slight increase of urine formation

• Postural changes affect renal functions

• extensive secretion of placental hormones ?

•Eclampsia - vascular spasms, chronic seizures, coma

Catabolic phase (accelerated starvation):

• Insulin resistance caused by HCS, cortisol and growth hormone

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

• Estrogen: growth of ductile system

Reproduction Block Physiology Wednesday, September

Reproduction Block Physiology Wednesday, September

Infant Empties Breast

Milk Production Occurs

Interference with this cycle decreases the milk

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