Sub : Obstetrics and Gynaecological

Nursing

A Class Presentation On
Physiological changes in
First and Second Stage of
Labor

Submitted to, Submitted by,

Madam I Tamang Shreya Putatunda
Clinical Instructor MSC. Nursing Part 1
CON,NBMCH CON,N BMCH
 What is Labor?

“Labor is series of events that takes place in the genital organs in an effort to expel
the viable product of. conception out of the womb through the vagina into the. outer
world.” - D.C.Dutta.

Conventionally , events of labor are divided into four stages;

 First Stage : It starts from the onset of true labor pain and ends with full dilation of cervix. It
is on other words , the Cervical Stage of Labor. It’s average duration is 12 hours for
primigravida and 6 hours for multiparae .

 Second Stage: It starts with full dilatation of cervix to end of expulsion of fetus from birth
canal. Its has two phases-
a. Propulsive Phase- Starting from full dilation to descent of presenting part to pelvic floor.
b. Expulsive Phase- Maternal bearing down effort and ends w2ith delivery of the baby.
It’s average duration is 2hours in primigravidae and 30 minutes in multigravida.

 Third Stage : It begins after expulsion of fetus and ends with expulsion of placenta and
membranes . Its average duration is about 15 minutes in both primi and multiparae. The
duration is however reduced to 5minutes in active management.

 Fourth Stage : It is the stage of observation for at least 1 hour after expulsion of the after
births. During this period general condition of patient and behavior of uterus carefully
monitored.

 Causes of Physiological Changes in Labor; The precise mechanism of initiation

of human labor is still obscure. Endocrine, biochemical and mechanical stretch pathways
as obtained from animal experiments, however, put forth the following hypotheses.

 Uterine distension: Stretching effect on the myometrium by the growing fetus and liquor
amnii can explain the onset of labor at least in twins or polyhydramnios. Uterine stretch
increases gap junction proteins, receptors for oxytocin and specific contraction associated
proteins (CAPs)
 Fetoplacental contribution: Cascade of events activate fetal hypothalamic-pituitary-
adrenal axis prior to onset of labor increased CRH → increased release of ACTH → fetal
adrenals - increased cortisol secretion → accelerated production of estrogen and
prostaglandins from the placenta.
 Estrogen: The probable mechanisms are:
 Increases the release of oxytocin from maternal pituitary
 Promotes the synthesis of myometrial receptors for oxytocin (by 100-200 folds),
prostaglandins and increase in gap junctions in myometrial cells.
 Accelerates lysosomal disintegration in the decidual and amnion cells resulting in
increased prostaglandin (PGF 2a) synthesis
 Stimulates the synthesis of myometrial contractile protein-actomyosin through CAMP
  Increases the excitability of the myometrial cell membranes.

 Progesterone: Increased fetal production of dehydroepiandrosterone sulfate (DHEA-S)

and cortisol inhibits the conversion of fetal pregnenolone to progesterone. Progesterone
levels therefore fall before labor. It is the alteration in the estrogen progesterone ratio
rather than the fall in the absolute concentration of progesterone, which is linked with
prostaglandin synthesis.

 Prostaglandins: Prostaglandins are the important factors, which initiate and maintain
labor. The major sites of synthesis of prostaglandins are-amnion, chorion, decidual cells
and myometrium. Synthesis is triggered by-rise in estrogen level, glucocorticoids,
mechanical stretching in late pregnancy, increase in cytokines (IL-1, 6, TNF), infection,
vaginal examination, and separation or rupture of the membranes. Prostaglandins enhance
gap junction (intermembranous gap between two cells through which stimulus flows)
formation.

 Physiological Alteration in Mother during Labor :

In labor the mother expends considerable energy. The energy expenditure increases
significantly during second stage , when voluntary efforts come into play. The metabolic
process supplying this energy requires glucose , and if there is an inadequate supply , fat is
broken down in place of glucose. As excessive oxidation of fat occurs , progressive
ketoacidosis develops, especially in prolonged labor. Significant degrees of physical
exhaustion are seen in the mother during the course of labor.
The increased energy requirement is not only due to increased uterine muscular activity, but
also due to increased cardiac output. The pulse rate increases , but rarely exceeds 100bpm,
Body temperature rises, but not more than 99.8 degree F . Profuse sweating and fluid loss
leads to dehydration and even Ketoacidosis. Early detection and adequate fluid replacement
is necessary.

The last few hours of human pregnancy are characterized by forceful and painful uterine
contractions that effect cervical dilatation and cause the fetus to descend through the birth
canal. There are extensive preparations in both the uterus and cervix long before this. During
the first 36 to 38 weeks of normal gestation, the myometrium is in a preparatory yet
unresponsive state.

Concurrently, the cervix begins an early stage of remodeling— termed softening—yet

maintains structural integrity. Following this prolonged uterine quiescence, there is a
transitional phase during which myometrial unresponsiveness is suspended, and the cervix
undergoes ripening, effacement, and loss of structural integrity.

Parturition can be arbitrarily divided into four overlapping phases that correspond to the
major physiological transitions of the myometrium and cervix during pregnancy. These
phases of parturition include:

(1) a prelude to it,

(2) the preparation for it,

(3) the process itself, and

(4) recovery.

Importantly, the phases of parturition should not be confused with the clinical stages of labor,
that is, the first, second, and third stages—which comprise the third phase of parturition.

■ Phase 1 : Uterine Quiescence and Cervical Softening

 Uterine Quiescence: Beginning even before implantation, a remarkably effective
period of myometrial quiescence is imposed. This phase normally comprises 95
percent of pregnancy and is characterized by uterine smooth muscle tranquility with
maintenance of cervical structural integrity. Concurrently, the uterus must initiate
extensive changes in its size and vascularity to accommodate the pregnancy and
prepare for uterine contractions. The myometrial unresponsiveness of phase 1
continues until near the end of pregnancy. Some low-intensity myometrial
contractions are felt during the quiescent phase, but they do not normally cause
cervical dilatation. Contractions of this type become more common toward the end of
pregnancy, especially in multiparous women, and are referred to as Braxton Hicks
contractions or false labor.

 Cervical Softening : The cervix has multiple functions during pregnancy that
include: (1) maintenance of barrier function to protect the reproductive tract from
infection, (2) maintenance of cervical competence despite increasing gravitational
forces, and (3) orchestration of extracellular matrix changes that allow progressive
increases in tissue compliance.
In non pregnant women, the cervix is closed and firm, and its consistency is similar to
nasal cartilage. By the end of pregnancy, the cervix is easily distensible, and its
consistency is similar to the lips of the oral cavity.

Thus, the first stage of this remodeling—termed softening—is characterized by an

increase in tissue compliance, yet the cervix remains firm and unyielding. Hegar first
described palpable softening of the lower uterine segment at 4 to 6 weeks’ gestation,
and this sign was once used to diagnose pregnancy.

Structural Changes with Softening: Cervical softening results from increased

vascularity, stromal hypertrophy, glandular hypertrophy and hyperplasia, and slow,
progressive compositional or structural changes of the extracellular matrix. During
matrix changes, collagen, the main structural protein in the cervix, undergoes
conformational changes that alter tissue strength and flexibility. Specifically, collagen
processing and the number or type of covalent cross-links between collagen triple
helices are altered. These cross-links are normally required for stable collagen fibril
formation.

A reduction in cross-links between newly synthesized collagen monomers results

from reduced expression and activity of the cross-link forming enzymes, lysyl
hydroxylase and lysyl oxidase, beginning in early pregnancy. Concurrently there is
reduced expression of the matricellular proteins thrombospondin 2 and tenascin C.

These proteins also influence collagen fibril structure and strength. Together, these
early pregnancy changes contribute to the gradual increase in tissue compliance
during pregnancy.
 Composite of the average dilatation curve for labor in nulliparous women. The curve is based on
analysis of data derived from a large, nearly consecutive series of women. The first stage is divided
into a relatively flat latent phase and a rapidly progressive active phase. In the active phase, there are
three identifiable component parts: an acceleration phase, a linear phase of maximum slope, and a
deceleration phase.

 Phase 2 : Preparation for Labor

To prepare for labor, the myometrial tranquility of phase 1 of parturition must be suspended
—so-called uterine awakening or activation. This phase 2 is a progression of uterine changes
during the last 6 to 8 weeks of pregnancy.

 Myometrial Changes : Myometrial changes prepare it for labor contractions. This

shift probably results from alterations in the expression of key proteins that control
contractility. These contraction associated proteins (CAPs) include the oxytocin receptor,
prostaglandin F receptor, and connexin 43. Together, these lead to increased uterine
irritability and responsiveness to uterotonins—agents that stimulate contractions. Another
critical change in phase 2 is formation of the lower
uterine segment from the isthmus. With this development, the fetal head often descends
to or even through the pelvicinlet—so-called lightening. There are also human studies
 that report an expression gradient of oxytocin receptors, with greater expression in fundal
myometrial cells.

 Cervical Ripening During Phase 2 : Before contractions begin, the cervix must
undergo more extensive remodeling. This eventually results in cervical yielding and
dilatation upon initiation of forceful uterine contractions. Cervical modifications during
this second phase principally involve connective tissue changes—so-called cervical
ripening. During this transformation, the total amount and composition of proteoglycans
and glycosaminoglycan within the matrix are altered.

 Cervical Connective Tissue:

Collagen: The cervix is an extracellular matrix-rich tissue. Constituents of the
matrix include type I, III, and IV collagen, glycosaminoglycans, matricellular proteins,
proteoglycans, and elastin. Of these, collagen is largely responsible for structural
disposition of the cervix. During cervical ripening, collagen fibril diameter is increased
and there is increased spacing between fibrils. These changes may result in part from
accumulation of poorly cross-linked collagen and reduced expression of matricellular
proteins.

Fibrillar collagen synthesis and organization

Proteoglycans : These glycoproteins are composed of a protein core and

GAG chains. Although not well-defined, changes in proteoglycan composition are
thought to accompany cervical ripening. In addition to the cervix, these proteoglycans
are expressed in the fetal membranes and uterus. Changes in expression levels may
regulate fetal membrane tensile strength and uterine function.

 Inflammatory Changes; The marked changes within the extracellular matrix during
cervical ripening in phase 2 are accompanied by stromal invasion with inflammatory
 cells. In phase 3 or 4 of parturition, there is increased cervical expression of chemokine
and collagenase/protease activity. There is a robust increase in proinflammatory and
immunosuppressive genes in the cervix after delivery compared with during cervical
ripening.

 Induction and Prevention of Cervical Ripening : There are no therapies to

prevent premature cervical ripening. Cervical cerclage is used to circumvent cervical
insufficiency, although success appears limited. treatment to promote cervical ripening
for labor induction includes direct application of prostaglandins E2 (PGE2) and F2α
(PGF2α). Prostaglandins likely modify extracellular matrix structure to aid ripening.

 Phase 3 of Parturition: Labor The first stage begins when spaced uterine
contractions of sufficient frequency, intensity, and duration are attained to bring about
cervical thinning, or effacement. This labor stage ends when the cervix is fully dilated—
about 10 cm—to allow passage of the term-sized fetus. The first stage of labor, therefore,
is the stage of cervical effacement and dilatation.

The second stage begins when cervical dilatation is complete and ends with delivery.
Thus, the second stage of labor is the stage of fetal expulsion. Last, the third stage begins
immediately after delivery of the fetus and ends with the delivery of the placenta. Thus,
the third stage of labor is the stage of placental
separation and expulsion.

 First Stage of Labor:

 Clinical Onset of Labor: Labor initiation is heralded by spontaneous release of a

small amount of blood-tinged mucus from the vagina. This extrusion of the mucus plug
that had previously filled the cervical canal during pregnancy is referred to as “show” or
“bloody show.”

 Uterine Labor Contractions : Uterine contractions are involuntary and, for the
most part, independent of extra uterine control. Mechanical stretching of the cervix
enhances uterine activity. This phenomenon has been referred to as the Ferguson reflex.
The interval between contractions diminishes gradually from approximately 10 minutes at
the onset of first stage labor to as little as 1 minute or less in the second stage. Periods of
relaxation between contractions, however, are essential for fetal welfare. Unremitting
contractions compromise uteroplacental blood flow sufficiently to cause fetal hypoxemia.
In active phase labor, the duration of each contraction ranges from 30 to 90 seconds,
averaging about 1 minute.
 Distinct Lower and Upper Uterine Segments: By abdominal palpation, even
before membrane rupture, the two segments can sometimes be differentiated. The upper
segment is firm during contractions,
whereas the lower segment is softer, distended, and more passive. This mechanism is
imperative because if the entire myometrium, including the lower uterine segment and
cervix, were to contract simultaneously and with equal intensity, the net expulsive force
would be markedly decreased. Thus, the upper segment contracts, retracts, and expels the
fetus. In response to these contractions, the softened lower uterine segment and cervix
dilate and thereby form a greatly expanded, thinned-out tube through which the fetus can
pass.

After each contraction of the upper segment, the muscles do not return to their previous
length, but tension remains essentially the same. By comparison, in the lower segment,
successive lengthening of the fibers with labor is accompanied by thinning, normally to
only a few millimeters in the thinnest part. As a result of the lower segment thinning and
concomitant upper segment thickening, a boundary between the two is marked by a ridge
on the inner uterine surface—the physiological retraction ring. When the thinning of the
lower uterine segment is extreme, as in obstructed labor, the ring is prominent and forms
a pathological retraction ring. This abnormal condition is also known as the Bandle ring.

Sequence of development of the segments and rings in the uterus at term and in labor

 Changes in Uterine Shape During Labor : Each contraction produces an

elongation of the ovoid uterine shape with a concomitant decrease in horizontal diameter.
This change in shape has important effects on the labor process. First, there is increased
fetal axis pressure, that is, the decreased horizontal diameter serves to straighten the fetal
vertebral column. This presses the upper pole of the fetus firmly against the fundus,
whereas the lower pole is thrust farther downward. The lengthening of the ovoid shape
has been estimated at 5 and 10 cm.
Second, with lengthening of the uterus, the longitudinal muscle fibers are drawn taut. As
a result, the lower segment and cervix are the only parts of the uterus that are flexible, and
these are pulled upward and around the lower pole of the fetus.
 The uterus at the time of vaginal delivery

 Cervical Changes : As the result of contraction forces, two fundamental changes

—effacement and dilatation—occur in the already-ripened cervix. For an average-sized
fetal head to pass through the cervix, its canal must dilate to a diameter of approximately
10 cm. At this time, the cervix is said to be completely or fully dilated. Although there
may be no fetal descent during cervical effacement, most commonly the presenting fetal
part descends somewhat as the cervix dilates. During second-stage labor in nulliparas, the
presenting part typically descends slowly and steadily. In multiparas, however,
particularly those of high parity, descent may be rapid.

Schematic showing effacement and dilatation

A. Before labor, the primigravid cervix is long and undilated in contrast to that of the multipara, which has
dilatation of the internal and external os. B. As effacement begins, the multiparous cervix shows dilatation and
 funneling of the internal os. This isless apparent in the primigravid cervix. C. As complete effacement is
achieved in the primigravid cervix, dilation is minimal.

Cervical effacement is “obliteration” or “taking up” of the cervix. It is manifest clinically

by shortening of the cervical canal from a length of approximately 2 cm to a mere circular
orifice with almost paper-thin edges. The muscular fibers at the level of the internal
cervical os are pulled upward, or “taken up,” into the lower uterine segment. l os remains
temporarily unchanged.

Effacement may be compared to a funneling process in which the whole length of a

narrow cylinder is converted into a very obtuse, flaring funnel with a small circular
opening. Because of increased myometrial activity during uterine preparedness for labor,
appreciable effacement of a softened cervix sometimes is accomplished before active
labor begins.

Effacement causes expulsion of the mucous plug as the cervical canal is shortened. Because
the lower segment and cervix have lesser resistance during a contraction, a centrifugal pull is
exerted on the cervix and creates cervical dilatation. Early rupture of the membranes does not
retard cervical dilatation so long as the presenting fetal part is positioned to exert pressure
against the cervix and lower segment. The process of cervical effacement and dilatation
causes formation of the forebag of amniotic fluid. This is the leading portion of fluid and
amniotic sac located in front of the presenting part.

 Second Stage of Labor:

 Fetal Descent : In many nulliparas, engagement of the head is accomplished before labor
begins. That said, the head may not descend further until late in labor. In the descent pattern
of normal labor, a typical hyperbolic curve is formed when the station of the fetal head is
plotted as a function of labor duration. Station describes descent of the fetal biparietal
diameter in relation to a line drawn between maternal ischial spines .

Active descent usually takes place after dilatation has progressed for some time . In
nulliparas, increased rates of descent are observed ordinarily during cervical dilatation phase
of maximum slope. At this time, the speed of descent is also maximal and is maintained until
the presenting part reaches the perineal floor .
 Pelvic Floor Changes during Labor ; The birth canal is supported and is functionally
closed by several layers of tissues that together form the pelvic floor. The most important are
the levator ani muscle and the fibromuscular connective tissue covering its upper and lower
surfaces. There are marked changes in the biomechanical properties of these structures and of
the vaginal wall during parturition. The levator ani consists of the pubovisceral, puborectalis,
and iliococcygeus muscles, which close the lower end of the pelvic cavity as a diaphragm.
During pregnancy, the levator ani usually undergoes hypertrophy, forming a thick band that
extends backward from the pubis and encircles the vagina about 2 cm above the plane of the
hymen. On contraction, the levator and draws both the rectum and the vagina forward and
upward in the direction of the symphysis pubis and thereby acts to close the vagina.

Labor course divided on the basis of expected evolution of the dilatation and descent curves into three functional
divisions. The preparatory division includes the latent and acceleration phases. The dilatational division is the
phase of maximum slope of dilatation. The pelvic division encompasses both the deceleration phase and the
second stage, which is concurrent with the phase of maximum slope of fetal descent

 PHYSIOLOGICAL AND BIOCHEMICAL PROCESSES

REGULATING STAGES OF LABOR:
There are two general contemporaneous theorems concerning labor initiation. The first is
the functional loss of pregnancy maintenance factors, whereas the second focuses on
synthesis of factors that induce parturition.
An obligatory role for one or more uterotonins is included in most parturition theories, as
either a primary or a secondary phenomenon in the final events of childbirth. Both rely on
careful regulation of smooth muscle contraction.
 Myometrial Action There are unique characteristics of smooth muscle, including
myometrium, compared with those of skeletal muscle that may
confer advantages for uterine contraction efficiency and fetal delivery. First, the degree of
smooth-muscle cell shortening with contractions may be one order of magnitude greater
than that attained in striated muscle cells. Second, forces can be exerted in smooth muscle
cells in multiple directions. In contrast, the contraction force generated by skeletal muscle
is always aligned with the axis of the muscle fibers. Third, smooth muscle is not
organized in the same manner as skeletal muscle. In myometrium, the thick and thin
filaments are found in long, random bundles throughout the cells. This plexiform
arrangement aids greater shortening and force-generating capacity. Last, greater
multidirectional force generation in the uterine fundus compared with that of the lower
uterine segment permits versatility in expulsive force directionality. These forces thus can
be brought to bear irrespective of the fetal lie or presentation.

 Intracellular Calcium ; Agents that promote contraction act on myometrial cells to

increase intracellular cytosolic calcium concentration—[Ca2+] Or, they allow an influx of
extracellular calcium through ligand- or voltage-regulated calcium channels .For
example, prostaglandin F2α and oxytocin bind their respective receptors during labor to
open ligand-activated calcium channels. Activation of these receptors also releases
calcium from the sarcoplasmic reticulum to cause decreased electronegativity within the
cell. Voltage-gated ion channels open, additional calcium ions move into the cell, and
cellular depolarization follows Conditions that decrease [Ca2+] and increase intracellular
concentrations of cyclic adenosine monophosphate (cAMP) or cyclic guanosine
monophosphate (cGMP) ordinarily promote uterine relaxation. Corticotropin-releasing
hormone is one of several factors reported to regulate [Ca2+] and subsequently modulate
expression of the large-conductance potassium channels (BKCa) in the human
myometrium .

In addition to myocyte contractility, myocyte excitability is also regulated by changes in

the electrochemical potential gradient across the plasma membrane. Before labor,
myocytes maintain a relatively high interior electronegativity. During uterine quiescence,
the maxi-K channel is open and allows potassium to leave the cell to maintain interior
electronegativity. At the time of labor, changes in electronegativity lead to depolarization
and Contraction.

 Myometrial Gap Junctions; Cellular signals that control myometrial contraction

and relaxation can be effectively transferred between cells through intercellular junctional
channels. Communication is established between myocytes by gap junctions, which aid
the passage of electrical or ionic coupling currents as well as metabolite coupling. The
 transmembrane channels that make up the gap junctions consist of two protein “hemi-
channels” . These connexons are each composed of six connexin subunit proteins . These
pairs of connexons establish a conduit between coupled cells for the exchange of small
molecules that can be nutrients, waste, metabolites, second messengers, or ions.

 Cell Surface Receptors ; There are various cell surface receptors that can directly
regulate myocyte contractile state. Three major classes are G-protein-linked, ion channel
linked, and enzyme-linked. Multiple examples of each have been identified in human
myometrium. These further appear to be modified during the phases of parturition.

The protein subunits of gap junction channels are called connexins. Six connexins form a hemichannel
(connexon), and two connexons (one from each cell) form a gap junction channel. Connexons and gap
junction channels can be formed from one or more connexin proteins. The composition of the gap junction
channel is important for their selectivity with regard to passage of molecules and communication between
cells

■ Phase 1: Uterine Quiescence and Cervical Competence

Human parturition and its quiescence are likely the result of many factors that include: (1)
actions of estrogen and progesterone via intracellular receptors, (2) myometrial cell
 plasma membrane receptor mediated increases in cAMP, (3) generation of cGMP, and
(4)other systems, including modification of myometrial-cell ion channels.

The key factors thought to regulate the phases of parturition. CRH =corticotropin-releasing hormone;
hCG = human chorionic gonadotropin; SPA = surfactant protein A.

 Progesterone and Estrogen Contributions;

In many species, the role of the sex steroid hormones is clear— progesterone inhibits and
estrogen promotes the events leading
to parturition. In humans, however, it seems most likely that
both estrogen and progesterone are components of a broaderbased molecular system that
implements and maintains uterine quiescence. In many species, the removal of
progesterone, that is, progesterone withdrawal, directly precedes progression of phase 1
into phase 2 of parturition. In all species studied to date, including humans, administration
of the progesterone-receptor antagonists mifepristone (RU-486) or onapristone will
promote some or all key features of parturition. These include cervical ripening, increased
cervical distensibility, and increased uterine sensitivity to uterotonins.
The exact role of estrogen in regulating human uterine
activity and cervical competency is less well understood. That
said, it appears that estrogen can act to promote progesterone .

 Myometrial Cell-to-Cell Communication;

Progesterone maintains uterine quiescence by various mechanisms that cause decreased
expression of the contraction-associated proteins (CAPs). Progesterone can promote
expression of the inhibitory transcription factor ZEB1—zinc finger E-box binding homeobox
protein 1—which can inhibit expression of the CAP genes, connexin 43, and oxytocin
receptor. As another mechanism, progesterone bound to the progesterone receptor (PR) can
recruit co-regulatory factors.

 G-Protein–Coupled Receptors;
These receptors together with appropriate ligands may act in concert with sex steroid
hormones as part of a fail-safe system to maintain uterine quiescence.

 Beta-Adrenoreceptors;
These receptors are prototypical examples of cAMP signaling causing myometrium
relaxation. Agents binding to these receptors have
been used for tocolysis with preterm labor and include ritodrine and terbutaline.

 Luteinizing Hormone (LH) and Human Chorionic

Gonadotropin (hCG) Receptors;
Levels of myometrial LH-hCG receptors during pregnancy are greater before than during
labor. This decreases contraction frequency and force and decreases the number of tissue-
specific myometrial cell gap junctions.
Thus, high circulating levels of hCG may be one mechanism causing uterine quiescence.

 Relaxin;
Although relaxin may contribute to uterine quiescence, it also has roles in phase 2 of
parturition. These include remodeling of the extracellular matrix of the uterus, cervix,
vagina, breast, and pubic symphysis as well as promoting cell proliferation and inhibiting
apoptosis. Its actions on cell proliferation and apoptosis are mediated through the G-
protein-coupled receptor, RXFP1,whereas some but not all actions of relaxin on matrix
remodeling are mediated through this receptor.
Relaxin promotes growth of the cervix, vagina, and pubic symphysis and is necessary for
breast remodeling for lactation.
 Fetal Contributions to Initiation of Parturition :
It is intellectually intriguing to envision that the mature human fetus provides the signal to
initiate parturition. This seems most logical because such a signal could be transmitted in
several ways to suspend uterine quiescence. The fetus may provide a signal through a blood-
borne agent that acts on the placenta.

 Uterine Stretch and Parturition;

In association with fetal growth, significant increases in myometrial tensile stress and
amniotic fluid pressure follow. With uterine activation, stretch is required for
induction of specific contraction-associated proteins . Specifically, stretch increases
expression of the gap junction protein—connexin 43 and of oxytocin receptors. Gastrin-
releasing peptide, a stimulatory agonist for smooth muscle, is increased by stretch in the
myometrium.
Cell signaling systems used by stretch to regulate the myometrial cell continue to be
defined. This process—mechano transduction—may include activation of cell-surface
receptors or ion channels, transmission of signals through extracellular matrix, or release
of autocrine molecules that act directly on myometrium.

 Fetal Endocrine Cascades Leading to Parturition;

The ability of the fetus to provide endocrine sign. This signal was shown to come from the
fetal hypothalamic pituitary-adrenal axis that initiate parturition has been demonstrated in
several species. Defining the exact mechanisms regulating human parturition has proven
more difficult, and all evidence suggests that it is not regulated in the exact manner seen in
the sheep.

Even so, activation of the human fetal hypothalamic-pituitary adrenal-placental axis is

considered a critical component of normal parturition. As in the sheep, steroid products of the
human fetal adrenal gland are believed to have effects on the placenta and membranes that
eventually transform myometrium from a quiescent to contractile state.
■ Fetal Lung Surfactant and Parturition;
Surfactant protein A (SP-A) produced by the fetal lung is required for lung maturation. Its
levels are increased in amnionic fluid at term in mice. This factor activates inflammatory
response genes in the myometrium, which in term promote uterine contractility. SP-A is
expressed by the human amnion and decidua, is present in the amnionic fluid, and prompts
signaling pathways in human myometrial cells.

 Fetal Anomalies and Delayed Parturition;

There is fragmentary evidence that pregnancies with markedly diminished estrogen

production may be associated with prolonged gestation. These “natural experiments” include
fetal anencephaly with adrenal hypoplasia and those with inherited placental sulfatase
deficiency. The broad range of gestational length seen with these disorders calls into question
the exact role of estrogen in human parturition initiation.

Other fetal abnormalities that prevent or severely reduce the entry of fetal urine into amnionic
fluid—renal agenesis, or into lung secretions—pulmonary hypoplasia, do not prolong human
pregnancy. Thus, a fetal signal through the paracrine arm of the fetal-maternal
communication system does not appear to be mandated for parturition initiation.

Some brain anomalies of the fetal calf, fetal lamb, and sometimes the human fetus delay the
normal timing of parturition.
 Phase 3: Uterine Stimulation

This parturition phase is synonymous with uterine contractions that bring about
progressive cervical dilatation and delivery. Current data favor the uterotonin theory of
labor initiation.
Increased uterotonin production would follow once phase 1 is suspended and uterine
phase 2 processes are implemented. A number of uterotonins may be important to the
success of phase 3, that is, active labor. Uterotonins that are candidates for labor
induction include oxytocin, prostaglandins, serotonin, histamine, PAF, angiotensin II, and
many others. All have been shown to stimulate smooth muscle contraction through G-
protein coupling.

 Oxytocin and Phase 3 of Parturition

Late in pregnancy, during phase 2 of parturition, there is a 50-fold or more increase in the
number of myometrial oxytocin receptors This increase coincides with an increase in
uterine contractile responsiveness to oxytocin. Moreover, prolonged gestation is
associated with a delay in the increase of these receptors .
Oxytocin—literally, quick birth—was the first uterotonin to be implicated in parturition
initiation. The prohormone is transported with its carrier protein, neurophysin, along the
axons to the neural lobe of the posterior pituitary gland in membrane-bound vesicles for
storage and later release. The prohormone is converted enzymatically to oxytocin during
transport. Because of successful labor induction with oxytocin, it was logically suspected
in parturition initiation. First, in addition to its effectiveness in inducing labor at term,
oxytocin is a potent uterotonin and occurs naturally in humans. Subsequent observations
provide additional support for this theory: (1) the number of oxytocin receptors strikingly
increases in myometrial and decidual tissues near the end of gestation; (2) oxytocin acts
on decidual tissue to promote prostaglandin release; and (3) oxytocin is synthesized
directly in decidual and extraembryonic fetal tissues and in the placenta .
Although little evidence suggests a role for oxytocin in phase 2 of parturition, abundant
data support its importantrole during second-stage labor and in the puerperium—phase 4
of parturition. Specifically, there are increased maternal serum oxytocin levels: (1) during
second-stage labor, which is
the end of phase 3 of parturition; (2) in the early puerperium; and (3) during breast
feeding.

 Prostaglandins and Phase 3 of Parturition;

First, levels of prostaglandins—or their metabolites—in amnionic fluid, maternal plasma,
and maternal urine are increased during labor. Second, treatment of pregnant women with
prostaglandins, by any of several administration routes, causes abortion or labor at all
gestational stages. Moreover, administration of prostaglandin H synthase type 2 (PGHS-
2) inhibitors to pregnant women will delay spontaneous labor onset and sometimes arrest
preterm labor .
During labor, prostaglandin production within the myometrium and decidua is an efficient
mechanism of activating contractions. For example, prostaglandin synthesis is high and
unchanging in the decidua during phase 2 and 3 of parturition. Moreover, the receptor level
for PGF2α is increased in the decidua at term, and this increase most likely is the regulatory
step in prostaglandin action in the uterus. The myometrium synthesizes PGHS-2 with labor
onset, but most prostaglandins likely come from the decidua.
The fetal membranes and placenta also produce prostaglandins. Primarily PGE2, but also
PGF2α, are detected in amnionic fluid at all gestational stages. As the fetus grows,
prostaglandins levels in the amnionic fluid increase gradually. Their major increases in
concentration within amnionic fluid, however, are demonstrable after labor begins . These
higher levels likely result as the cervix dilates and exposes decidual tissue .These increased
levels in the forebag compared with those in the upper compartment are believed to follow an
inflammatory response that signals the events leading to active labor.

Mean (±SD) concentrations of prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) in amnionic fluid at
term before labor and in the upper and forebag compartments during labor at all stages of cervical dilatation

■ Endothelin-1 ; Endothelin-1 is produced in myometrium of term gestations and is able

to induce synthesis of other contractile mediators such as prostaglandins and inflammatory
mediators .The requirement of endothelin-1 in normal parturition physiology remains to be
established.

■ Angiotensin II;
There are two G-protein-linked angiotensin II receptors expressed in the uterus—AT1 and
AT2. In non-pregnant women, the AT2 receptor is predominant, but the AT1 receptor is
preferentially expressed in pregnant women .Angiotensin II binding to the plasma-membrane
receptor evokes contraction. During pregnancy, the vascular smooth muscle that expresses
the AT2 receptor is refractory to the pressor effects of infused angiotensin II .

■ Contribution of Intrauterine Tissues to Parturition ;

Although they have a potential role in parturition initiation, the amnion, chorion laeve, and
decidua parietalis more likely have an alternative role. The membranes and decidua make up
an important tissue shell around the fetus that serves as a physical, immunological, and
metabolic shield to protect against untimely initiation of parturition.

Amnion: Virtually all of the tensile strength—resistance to tear .Several bioactive peptides
and prostaglandins that cause myometrial relaxation or contraction are synthesized in amnion.
Late in pregnancy, amnionic prostaglandin biosynthesis is increased, and phospholipase A2
and PGHS-2 show increased activity . Accordingly, many hypothesize that prostaglandins
regulate events leading to parturition. It is likely that amnion is the major source for amnionic
fluid prostaglandins, and their role in activation of cascades that promote membrane rupture
is clear. The influence of amnion-derived prostaglandins on uterine quiescence and
activation, however, is less clearing and rupture—of the fetal membranes is provided by the
amnion.

Chorion Laeve: This tissue layer also is primarily protective and provides immunological
acceptance. The chorion laeve is also enriched with that inactivate uterotonins. Enzymes
include prostaglandin dehydrogenase (PGDH), oxytocinase, and enkephalinase . As noted,
PGDH inactivates amnion derived prostaglandins. With chorionic rupture, this barrier would
be lost, and prostaglandins could readily influence adjacent decidua and myometrium.

Decidua:A metabolic cocontribution of decidual activation to parturition initiation is an

appealing possibility for both anatomical and functional reasons. The generation of decidual
uterotonins that act in a paracrine manner on contiguous myometrium is intuitive. In addition,
decidua expresses steroid metabolizing enzymes such as 20α-HSD and steroid 5αR1 that may
regulate local progesterone withdrawal. Decidual activation is characterized by increased
proinflammatory cells and increased expression of proinflammatory cytokines,
prostaglandins, and uterotonins such as oxytocin receptors and connexin 43.
Conclusion : It is likely that multiple and possibly redundant processes contribute to the
success of the three active labor phases once phase 1 of parturition is suspended and phase 2
is initiated. Phase 3 is highlighted by increased activation of G-protein-coupled receptors that
inhibit cAMP formation, increase intracellular calcium stores, and promote interaction of
actin and myosin and subsequent force generation. Simultaneously, cervical proteoglycan
composition and collagen structure are altered to a form that promotes tissue distensibility
and increased compliance. The net result is initiation of coordinated myometrial contractions
of sufficient amplitude and frequency to dilate the prepared cervix and push the fetus through
the birth canal. Multiple regulatory ligands orchestrate these processes and vary from
endocrine hormones such as oxytocin to locally produced prostaglandins.

 Bibliography :

1. F. Gary Cunningham,Kenneth J. Leveno,Steven L. Bloom,Catherine Y. Spong,Jodi S.

Dashe,Barbara L.Hoffman,Brian M. Casey,Jeanne S. Sheffiel; Williams
OBSTETRICS, New Delhi, 24th Edition; Page; 408-29
2. Raman AV; Maternity Nursing. Lippincott Williams& Wilkins, Wolter Kluwer; New
Delhi; 19th Edition; Page; 461-466
3. Dutta DC; Textbook of Obstetrics, New Central Book Agency(p) Ltd. 7 th Edition;
Page;128-44