PHYSIOLOGY OF THE UTERINE MUSCLE DURING
LABOR
The uterus in prepared for labor by progressive morphological and functional
changes during pregnancy (chapter 13). Hypertrophy and dilatation (with limited
appearance of new muscle cells) as well as changes in connective tissue, blood vessels,
lymphatics and nerves have, beyond accommodation of fetus, one major aim: to make
ready the organ for the work and mechanics of delivery. There is a high degree of morphofunctional integration: muscular cells are changed, the whole environment is adapted and
the connective tissue ensures the transmission of contraction.
Estrogens stimulate uterine hyperplasia / hypertrophy. Together with progesterone
and chronic myometrial stretching (due to the fetal growth), they stimulate actomyosin and
collagen synthesis in a synergic manner.
I. MYOMETRIAL CELL AT TERM
At term, the myometrial cell is hypertrophied (500µm in length), has an ectopic
nucleus and, importantly, myofilaments consisting of actin and myosin. The plasma
membrane contains gap functions (for intercellular communication for synchronization) and
3 type of receptors:
1. Type I
- ion channels;
2. Type II
- GTP-binding protein as transducer; inositol triphosphate,
diacylglyceride or arachidonic acid as second messenger;
3. Type III
- enzymatic.
II. CELLULAR BASES OF CONTRACTILE ACTIVITY
Myosin is made of multiple light and heavy chains disposed in thick myofilaments.
Calmodulin (a calcium-binding regulatory protein) binds Ca2+. The resulting complex
activates the myosin light-chain kinase, which phosphorylates inactive light-chain myosin
(20kd) into the active P-myosin light chain (fig. 18.1).
Myosin light chain
Myosin light-chain kinase
 
(Ca2+ activated - calmodulin)
P-Myosin light chain
Ca2+  Troponin Tropomyosin  Actin
P-Actomyosin (ATPase)
ATP


ADP
Figure 18.1. Molecular bases of contraction
Ca2+ stimulates conversion of troponin in tropomyosin, which “prepares” actin. Pmyosin interacts with actin. The resulting molecule, P-actomyosin, is an ATPase that
catalyses ATP hydrolysis and liberation of energy, therefore contraction force.
III. CONTROL OF MYOMETRIAL CONTRACTILITY
There is a multifactorial initiation and control of uterine contraction:
Intracellular free Ca2+ (Ca2+i) is essential for myometrial contraction: modulation
of myosin light-chain kinase and conversion of troponin. The decrease of calcium
concentration promotes myometrial relaxation. Ca2+i is regulated by:





cell membrane channels-receptor / voltage-mediated;
cell membrane Na+-Ca2+ exchange pump;
cell membrane calcium ATPase system;
cell membrane and sarcoplasmic reticulum active Ca 2+ pumps;
cAMP and cGMP, which decrease Ca2+i;
Estrogens are necessary for myometrial receptor expression and intracellular
calcium release. On the opposite, progesterone stimulates calcium uptake by the
sarcoplasmic reticulum.
Oxytocin is a nanopeptide - the most specific uterotonic hormone. It is
synthesized in the magnocellular neurons of the supraoptic and paraventricular neurons
and transported, as prohormone, bound to the carrier protein (neurophysin), through neural
axons to the posterior pituitary gland. During transport, the prohormone is converted
enzymatically to oxytocin. It is, consecutively, stored in membrane-bound vesicles for later
release. Oxytocin has a specific receptor, which is present in myometrial cells after 12-13
weeks and increases to its maximum at term. Oxytocin opens voltage-mediated calcium
channels and prevents the sarcoplasmic calcium uptake, thus increasing Ca2+i and
promoting contraction. It also stimulates prostaglandin release.
Endothelin-1 acts similarly in way and magnitude with oxytocin, by opening the
voltage-mediated calcium channels and promoting prostaglandin release.
Prostaglandins have two ways of action:
1. PGE1, PGE2 and PGF2 (each with a specific receptor) alter membranes’
permeability for calcium and increase Ca2+i. On the opposite, PGD2 and
PGI2 (through specific receptors which use GTP-binding proteins) activate
intracellular adenyl cyclase, which increases CAMP and, subsequently,
reduces Ca2+i.
2. Concerning modulation of the gap junction formation, PGE1, PGE2 and PGF2
promote it (whereas PGI2 inhibit it).
Gap junctions play a key role in the coordination (thereby increasing the force) of
the contraction. Their structure has been described in chapter 13. They significantly
increase before labor (promoted by estrogens, PGE 1, PGE2 and PGF2). Progesterone
antagonizes estrogen effect.
Parathyroid hormone-related protein is increased, especially in the uterine
horns at term. It may stimulate local blood irrigation and uterine contraction, through
activation of adenylcyclase.
Calbindin D - 9 K is increased and plays a role in calcium transport.
Transforming growth factor- is increased and stimulates PTH-rP.
IV. INITIATION OF LABOR
During the last trimester of pregnancy, the process of cervical maturation is
accelerated, under the influence of the relaxin, placental hormones and PGE 2. During the
last weeks of gestation, there is an increased production of PGE2 and oxytocin receptors.
The concentration of oxytocin receptors increases with uterine distention. Concomitantly,
there is increase in the number of myometrial gap junctions. As a result of the increase in
oxytocin receptors and myometrial gap junctions, the myometrium becomes more reactive
to the oxytocin pulses secreted by the posterior pituitary, which then causes an
augmentation in the frequency and intensity of the contractions. The uterine contractions
generate greater pressure on the cervix, which further increases the production of PGE 2.
This results in an increased frequency of oxytocin pulses with subsequent more frequent
contractions (Ferguson reflex). The decidua also reacts to oxytocin by secreting PGF 2,
which increases the myometrial response to oxytocin.
At this point, placental and fetal maturational changes - as well as, possibly, the
stress of the transient fetal hypoxia related to the higher uterine contractility - induce the
secretion of a high number of substances, from several organs. This includes epidermal
growth factor, platelet-activating factor, adrenocorticotropic hormone, stress hormones,
vasopressin and increased amounts of oxytocin. There is a resulting greater mobilization of
arachidonic acid from the uterine phospholipids with a subsequent increase in
prostaglandin secretion from the placental membranes, especially during the contractions.
Prostaglandins, in turn, further stimulate the uterine contractility. The circle closes - and
this continuous self-enhancing cycle results in the initiation and sustaining of labor.
V. MYOMETRIAL CONTRACTILITY
Cellular, anatomical and physiological characteristics of myometrial muscle induce
unique features for increasing the efficiency of uterine contractions and of the delivery
mechanics:
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The contraction may be of one order of magnitude greater than that attained in
striated muscle cells;
Forces can be exerted in any direction;
Intracellular arrangement of thin and in thick filaments / long, random bundles
induces greater shortening / higher force-generating capacity;
The network disposal and the spindle shape of the myometrial cells allow
multidirectional force generation.
VI. UTERINE CONTRACTIONS DURING LABOR.
During labor, uterine contractions have some unique characteristics among
physiological muscular contractions, which represent some main labor diagnostic and
monitoring criteria:
1. Uterine contractions of labor are painful. The causes of the pain are:
 hypoxia of the contracted myometrium (as in angina pectoris);
 compression of nerve ganglia in the lower uterus and cervix;
 stretching of the cervix during dilatation;
 stretching of the peritoneum overlying the fundus.
2. Uterine contractions are involuntary.
3. The interval between contractions diminishes gradually from about 15-20
minutes before labor (false labor), 10 minutes at the onset of the first stage of
labor to as little as 2 minutes or less during the second stage.
4. The duration of each contraction progressively increases and ranges, in the
active phase, 30-90 seconds, averaging about 50 seconds.
5. The intensity of uterine contractions gradually rises (on average). From
around 20 mmHg before labor (Braxton Hicks), the intensity (25 mmHg at the
beginning of labor) augments to about 40 mmHg, with variation from 20 to 60
mmHg. It is elevated to 100-140 mmHg during expulsion (also increased by
maternal abdominal muscles during pushing) and even more, to 250 mmHg,
in the immediate puerperium.
Uterine relaxation between contractions is essential to the fetal welfare, as it
significantly influences uteroplacental and fetal–placental blood flow. Baseline pressure
increases from latent labor (less than 5 mmHg), but it should remain beneath certain
values: less than 12 mmHg during the active phase and less than 20 mmHg during the
second stage of labor.
VII. DIFFERENTIATION OF UTERINE ACTIVITY DURING LABOR
Uterine contractions have a necessary downward direction. The decreasing
contractile activity from fundus to cervix is necessary for a greater contractile force and for
the obvious directing of fetus towards the birth channel. From this point of view, the uterus
expresses two morpho-functional different parts:
1. The upper, active, segment contracts, retracts and becomes thicker as labor
advances. Successive contractions begin where the previous ones finished
and, through progressive retraction, uterine walls keep contact with the fetus.
The upper uterine segment becomes maximally thickened immediately after
fetal expulsion.
2. The lower, passive, portion is made of the lower uterine segment and the
cervix. It progressively develops during pregnancy from the isthmus, to a thin
(few millimeters in the thinnest part), distended channel for the fetus. The
relaxation is, however, not complete - and the progressive stretching with
subsequent lengthening is accompanied by a constant tension in the
muscular fibers.
The synchronism between the two uterine portions during labor is essential.
While the lower segment is distended because of the pressure exerted by the fetus pushed by the upper segment, this latter one can only contract / retract if the lower uterine
portion allows it. It follows, by lower segment distension / cervical dilatation, the fetal
passage.
Because of the significantly different morphological changes in the two portions,
the physiological retraction ring (a ridge between the two segments) appears on the inner
uterine surface.