Physiology of Labor

Prepared by:
Dr. Yobed.M. J, OBGYN- R1- Resident

Moderator:
Dr. Angesom.K , OBS/ GYN- SPECIALIST
 CONTENTS

I. THEORIES OF INITIATION OF LABOR

II. MATERNAL AND FETAL COMPARTMENTS
III. SEX STEROID HORMONE ROLE
IV. PROSTAGLANDINS ROLE
V. PHASE 1: UTERINE QUIESCENCE AND CERVICAL SOFTENING
VI. PHASE 2: PREPARATION FOR LABOR
VII. PHASE 3: LABOR
VIII. UTEROTONINS IN PARTURITION PHASE 3
IX. PHASE 4: THE PUERPERIUM
 3-major theories of initiation
1. functional loss of pregnancy maintenance factors
2. synthesis of factors that induce parturition
3. Fetus is the source of the initial signal
 Physiology of labor

• Has not been completely elucidated

• Labor is species specific
• Mechanism in humans is unique
1. Hormonal factors
a) Estrogen theory
b) Progesterone withdrawal theory
c) Prostaglandins theories
d) Oxytocin theory
e) Fetal cortisone theory
 Physiology of labor

2. Mechanical factors:
a) Uterine distension theory
b) Stretch of the lower Ux segments
Ferguson reflex
 MATERNAL COMPARTMENTS

UTERUS

Terminal differentiation not

phenotypic plasticity cell growth, proliferation,

secretion, and contractility
smooth muscle cell ↑↑
shortening with
contractions
Force exerted ←↑→↓

Muscle arrangements Plexiform=

thick and thin filament
bundles are long and
random
 MATERNAL COMPARTMENTS

Endometrium => decidua

• stromal cells and maternal immune cells
• Unique immunoregulatory functions
Cervix
• barrier function Ꝙ infection
• cervical competence Ꝙ gravity
• ↑Compliance ∑ extracellular matrix
 M/F compartment

Placenta
• exchange of nutrients and waste
• steroid hormones, growth factors, and other mediators
The fetal membranes and adjacent decidua
 Physiological shield
 immunological shield
 metabolic shield
 Fetal- compartment

amnion
 a selective filter
 Avascular
 resistant to leukocytes, microorganisms, and neoplastic
The chorion
 protective tissue layer
 provides immunological Acceptance
• Inactivating enzymes such as prostaglandin dehydrogenase,
oxytocinase, and enkephalinase
Aminion
chorion
desudua
Aminion => ↑ prostaglandins
phospholipase A2
PGHS-2
Chorion => ↓ pgn transfer
↑PGDH
but in labor ↓ PGDH =>
amnion-derived
prostaglandins can
influence membrane rupture
and uterine contractility
 SEX STEROID HORMONE ROLE

• both estrogen and progesterone => uterine quiescence

• ↑ P:E ratio- maintain pregnancy
• ↓ P:E ratio- parturition
• Estrogen ↑ progesterone responsiveness => uterine
quiescence
• estrogen aids processes that mediate uterine activation and
cervical ripening
• Both binds to nuclear receptors that regulate gene
transcription in a cell- and context-specific pattern
• ERα and ERβ, PR-A and PR-B
 PROSTAGLANDINS ROLE

• contractility Esterified arachinoic acids

Phospholipase A2 Phospholipase C
• relaxation
• inflammation arachinoic acid
• G-protein- coupled PGHS-1 (COX-1) PGHS-2 (COX-2)
receptors
• Isomerase is tissue PG-G 2→PG-H 2
specific PG- Isomerase PG- Isomerase
• ↑PGDH in pregnancy
Prostaglandins (PGE₂, PGF₂ α,PGI₂
• Synthesis Vs metabolism 15-hydroxyPGDH 15-hydroxyPGDH
• Expression of receptors is
relative
• switch in receptor-signaling Inactive metabolites
pathways
 Parturitions

• Phases of parturisions
1. A prelude to it
2. The preparation for it
3. The process it self
4. Recovery
clinical stages of labor 
phase 3 of parturition
Phases of labor from gabbe 7th edition
not used in this presentation
 PHASE 1: UTERINE QUIESCENCE AND CERVICAL
SOFTENING

• 95 % of pregnancy
• Why quiecence?
• neural, endocrine, paracrine, and autocrine
• “ fail-safe” system
• relative uterine unresponsiveness/ sielence
 estrogen and progesterone
 cAMP ↑
 cGMP ↑
 Modification of ion channels
 Uterine Relaxation & contraction

• Steroid and peptide hormones => Receptor => gene=>

proteins
• Quiescence
 ↓ IC- cross talk
 ↓ Ca2+
 Ion channel regulation
 ERSUPR
 Uterotonin degradation
• Contraction- the opposite
Ux Smooth muscle
Unitary Smooth Muscle
hundreds to thousands of
smooth muscle fibers
contract together as a single unit
Actin & myosin
Calmodulin
dense bodies
Less regular
 non-nervous stimuli
Prolonged tonic contraction
Slow Cycling of the Myosin Cross-
Bridges
Less energy but Greater force of conc
“latch” mechanism
Myometrial Relaxation and Contraction
Actin-Myosin Interactions
 Regulation of Membrane Potentials
Quiescence
Hyper polarization/ ↑ electronegativity
Large conductance voltage
Ca²⁺ activated K channels ( BKCa²⁺ )
Temporal expression of BKca2+ channels
Opening BKCa²⁺ → K+ leave the cell
↓ BKCa²⁺ channels → contractility
Myometrial Gap
Junctions
 synchrony b/n cells
Electrical coupling
Ionic coupling
Metabolite coupling
2 connexnons
6 connexins
Connexin- 43
Nutrients, waste,
metabolitis, ions, 2nd
messangers
 ↑ @ labor onset
 Endoplasmic Reticulum Stress Response (ERSR)

Uterine quiescence
Progesterone => caspase 3
degrades both actin and the specific gap
junction protein, connexin-43
 G-Protein–Coupled Receptors

• Signal transduction pathway

• Modified during phases of parturition
• Gi ɑ
• Gsɑ
• Gqɑ
• GTP-ɑ complex activate effector pathways such as

o adenyl cyclase
oPhospholipase
oIon channels
oKinase Fx
Quiescence with Gsɑ
EP₂ & EP₄
LH, HCG- receptors
β- adrenergic receptors
CRH
RELAXIN

Labor with Giɑ & Gqɑ

EP1 & EP3
CRH
 Cyclic Guanosine Monophosphate

• cGMP – relaxation
• Intracellular cGMP levels are increased in the
pregnant myometrium
• Atrial natriuretic peptide (ANP), Brain natriuretic peptide
(BNP) receptors, and nitric oxide
• All of these factors and their receptors are expressed
in the pregnant uterus
 Accelerated Uterotonin Degradation

• increased in phase 1
• decrease late in gestation
o PGDH => prostaglandins
o enkephalinase=> endothelins
o oxytocinase => oxytocin
o diamine oxidase => histamine
o catechol O-methyltransferase => catecholamines
o angiotensinases => angiotensin-II
o platelet-activating factor (PAF) and PAF acetylhydrolase
 Decidua

• Prostaglandin synthesis is suppressed, in particular PGF2α

• suppression withdrawal is a prerequisite for parturition
• immune tolerance to protect the fetus
• Epigenetic silencing of T cell–attracting inflammatory
chemokine genes
 Cervical Softening

Hegar’s sign
increased vascularity
cellular hypertrophy and hyperplasia
• extracellular matrix ∆
• by conformational ∆ on collagens
↓ cross-link-forming enzymes
↓ lysyl hydroxylase
↓ lysyl oxidase
• Cirvical insufficience in Ehlers-Danlos and Marfan syndromes
 PHASE 2: PREPARATION FOR LABOR

• Last few weeks of Px

• Ux awakening
• How??
• Progesterone withdrawal? In mammals
• Classic progesterone withdrawal resulting from decreased
secretion does not occur in human parturition
But in humans
 PHASE 2: PREPARATION FOR LABOR

Functional Progesterone Withdrawal

↓ activity of progesterone receptors
Area of active research
a. Relative expression of receptors PR-A, PR-B, PR-C
b. Differential interaction
c. Local inactivation/ natural antagonists
 PHASE 2: PREPARATION FOR LABOR

Myometrial ∆
o CAPs expressed
oxytocin receptors
gap junction proteins
o uterine irritability and responsiveness to uterotonins
 PHASE 2: PREPARATION FOR LABOR

Myometrial ∆
• lower uterine segment from the isthmus
• Fetal head descends to pelvic inlet
• Called “Lightening”
• Patient may complain “the baby dropped”
o Near term, HoxA13 gene in the lower myometrial segment
expressed
o Regionalized contractility of lower segment
 PHASE 2: PREPARATION FOR LABOR

Oxytocin Receptors
• Oxy receptors ↑
• Progesterone and estradiol appear to be the primary
regulators of oxytocin receptor expression
• Estrogen => enhance oxytocine receptors
• Progestrone => degradation of of oxyt receptors
 Cervical Ripening

softening =>> ripening

• relaxin regulates myometrial quiescence
• It also regulates cervical ripening
• Internal os= 50% smooth muscle
• External os= 10% >> >> >> >>
 Cervical Connective Tissue

• cervix is an extracellular-matrix-rich tissue

• type I, III, and IV collagen
• matricellular proteins
• glycosaminoglycans, proteoglycans, and elastic fibers
• Higher turnover of collagen
• replacement of mature cross-linked collagen fibrils with
poorly cross-linked fibrils, which yield greater collagen
disorganization
 Cervical Connective Tissue

• lysyl oxidase is the cross linker

• decorin or biglycan, thrombospondin 2
• increased turnover, rather than loss of collagen to achieve
cervical remodeling
• Hyaluronan
• leucine-rich proteoglycans are expressed in the cervix—
decorin, biglycan, and fibromodulin
 Cervix

• resident immune cells are localized to the cervical stroma

• little rise in proinflammatory gene expression
• leukocyte migration but not activation takes place before
labor
 Endocervical Epithelia

• endocervical glands
• a mucosal barrier and a tight junctional barrier that protect
against microbial invasion
• antimicrobial peptides and protease inhibitors
 Fetal Contributions to Parturition

a. Uterine Stretch ( mechanical transduction)

CAPs
• connexin-43
• oxytocin receptors
• gastrin-releasing peptide
 Fetal Contributions to Parturition

b. Fetal Endocrine Cascades

• Human- fetal HPAP- axis
• CRH- produced by the placenta
• Not governed by negative feedback
• But a feed-forward endocrine cascade
• Cortisone stimulate placental CRH- production
• Maternal CRH rise in 3rd tm
• CRH-BP ( binding protein)
• @ the end CRH-BP decrease thus the CRH action is increased
 Fetal Contributions to Parturition
c. Fetal lung
o SP-A, inhibit PGF₂ɑ
o Platelet activating factors, uterotonic
Decidua & aminion
o SP-A, inhibit PGF₂ɑ
 Fetal Contributions to Parturition

d. Fetal membrane senescence

o Physiologic aging
o Sterile inflammation
o SASP
( senescent-associated secretory phenotype)
 PHASE 3: LABOR

FIRST- stage: clinical onset of labor

• “show” or “bloody show” blood-tinged mucus from the
vagina
• painful
(1) hypoxia
(2) compression of nerve ganglia in the cervix and lower uterus
(3) cervical stretching
(4) stretching of the peritoneum
 PHASE 3: LABOR

Ferguson reflex
 oxytocine ↑
 PGF₂ɑ ↑
• Cervical “stripping” ↑ PGF₂α
 PHASE 3: LABOR

Distinct lower & upper Ux- segments

• Upper is firm during contraction
• Lower is soft and distended
• Upper contract and expel
• Lower is the thinned out tube for passage
• Muscle do not return to previous length
• But tension remains the same
segments and rings in the uterus
Hydrostatic actions of membranes in effecting cervical dilatation
Second stage
o Fetal descent
o Station- BPD in relation to ischial
spine
o Hyperbolic curve
 Pelvic floor changes

Levator ani and its fascia

Support
Stretched and thinned
Vaginal wall stretched and thinned
Perineum is also thinned
Anus dilate to 2- 3 cms
 3rd stage

Delivery of the placenta and membranes

 shultze mechanisim
=> Separation is 1st central
 Duncon mechanism
=> Separation is 1st peripheral
 UTEROTONINS IN PARTURITION PHASE 3

Oxytocin
(1) during second-stage labor
(2) in the early puerperium
(3) during breastfeeding
Prostaglandins
PGE2 and PGF2α
Endothelin-1
Angiotensin II
• G- protein coupled
• Both AT 1 & AT 2 EXPRESSED
• AT 1- predominate in gravidas
• AT 2- prredominate in non pregnant
• Blood vessels expressing AT 2 are resistant to angiotensin II
 PHASE 4: THE PUERPERIUM

• Just after labor for 1 hour

• myometrium remains persistently contracted
• endogenous and pharmacological uterotonic agents
• prevent hemorrhage
• Uterine involution
• Marked rise in proinflammatory & immunosupressive gene
expression
• cervical repair
• lactogenesis and milk let-down begin in mammary glands
• Ovulation generally occurs within 4 to 6 weeks after birth
 Labor physiology
summary
No body knows the exact mechanisms of labor initiation but
theories exist

1. functional loss of pregnancy maintenance factors

2. synthesis of factors that induce parturition

3. Fetus as a source of the initial signal???

REFERENCES

Williams25th edition
th
Gabbe 8 edition
Guyton 11th edition
I THANK YOU ALL
4 UR ATTENSION