Uterine smooth muscle activity in the non-pregnant
state
The uterus acts as a temporal receptacle which nurtures and nourishes
the implanted blastocyst while thwarting early expulsion of the product
of conception throughout pregnancy. It is a contractile smooth muscular
organ made up of fibrous connective tissue (37) that exhibits
spontaneous and rhythmic contraction and relaxation before, during and
after pregnancy(38,39). The non-pregnant uterus is not totally a
quiescent organ and exhibit intrinsic contractile properties. However,
contractions in the non-pregnant uterus vary physiologically from the
uterine contractile activities during pregnancy(40). Accordingly, both
non-invasive intrauterine pressure (IUP) and invasive ultrasound (US)
scan recordings have demonstrated that the non-pregnant uterus undergoes
patterns of phasic wave-like contractions throughout the menstrual
cycle(39,41–45) which are governed by ovarian steroid hormones (i.e.
oestrogen and progesterone)(38). Within the subendometrial layer of the
myometrium, cyclic patterns of oestrogen and progesterone receptors are
expressed which modulate the activity of the non-pregnant uterus(38,44).
These wave-like contractile patterns of the non-pregnant human uterus
vary depending on the phase of the menstrual cycle(figure 2) (42,44).
The rhythmic uterine contractions in the non-pregnant uterus favours
sperm transport and oocyte migration in the fallopian tubes,
fertilization and embryonic transport from the tubes into the uterine
cavity to facilitate embryonic nidation and implantation to
occur(39,41,42,44). Disruptions in this physiological uterine smooth
muscle property are associated with disorders such as dysmenorrhoea,
spontaneous and recurrent abortions, endometriosis, implantation
failures and infertility(42,44).
During menstruation or early follicular phase, the uterus exhibits
primarily antegrade (from fundus to cervix) labour-like and expulsive
contractions (figure 2) involving all layers of the myometrium to
evacuate the content of the uterus (menses). Uterine contractions during
menstruation are often felt and can be associated with blunt pain
(dysmenorrhoea) requiring medications if contractions are
vigorous(44,45). This period of luteofollicular changeover is largely
under the influence of progesterone depletion due to spontaneous
degeneration of the corpus luteum and increased gene expression for
prostaglandins by uterine tissues (figure 2) (39,45). In both mid and
late follicular phase of the menstrual cycle, only the subendometrial
layer exhibits a progressive increased in wave-like uterine contraction
patterns which are retrograde (from cervix to fundus) (figure 2). This
retrograde uterine contractions, often not perceived by the woman,
coupled with proliferation of endometrial glands which aid the transport
of sperm towards the distal end of the fallopian tubes where
fertilization takes place and normally terminates at the pre-ovulatory
period(41,42,44–46). These wave-like contractions and glandular
proliferation during the follicular phase are controlled by increased
oestrogen (E2) levels (figure 2) (41,42,44,46) indicative of oestrogen
predominance in the proliferative phase of the uterine cycle.
The post-ovulation period is characterized by progressive uterine
quiescence facilitated by significant rise in progesterone levels
following the successful development of the corpus luteum from the
ruptured ovarian follicle which terminates at the middle of the luteal
phase (figure 2). This luteinisation associated uterine quiescence
promotes successful establishment of pregnancy characterised by
embryonic transfer from the fallopian tube into the endometruim
depending on the biochemical readiness of the endometruim for
implantation of the embryo and placentation(39,41,42,46). Following
implantation, the uterus is transitioned from a non-pregnant state to a
pregnant milieu (figure 2) which allows the developing blastocyst to
differentiate into the foetal membranes comprising rich in connective
tissues in both the amnion and the chorion(47). The connective tissue
extracellular matrix of the amniochorion contains collagen fibres that
maintain the tensile strength of the amniochorion; resisting mechanical
stress and prevents rejection of the foetal allograft. Specific collagen
fibres of the fibrous connective tissue within the amniotic compact
layer provide the tensile strength while collagen fibres of both
reticular and spongy layers of the chorion provide mechanical
support(47). The major types of collagen fibres include: type I, II,
III, IV, V and VI collagens which are embedded in the fibrous
tissue(47).
Typically, the inner layer of the placenta is made up of the amniontic
membrane which is composed of amnion and chorion. The amnion has five
separate layers; the epithelium, basement membrane, compact layer,
fibroblast layer and spongy layer(48,49). The epithelium which consists
of a single layer of epithelial cells is proximal to the developing
foetus. The basement membrane of the amnion is a thin layer composed of
collagens III and IV and noncollagenous glycoproteins laminin, nidogen,
and fibronectin. The compact layer is dense nearly without cells and
forms the main fibrous structure of the amnion. The fibroblast layer of
the amnion is the thickest and consists of fibroblasts embedded in a
loose collagen network with abundance of noncollagenous glycoproteins.
The outermost spongy layer forms the interface between the amnion and
chorion and composed of a nonfibrillar meshwork of collagen III and an
abundant content of proteoglycans and glycoproteins(48,49).
The chorion is made up of a reticular layer, basement membrane and
trophoblast layer which is adhered to the maternal decidua. The
reticular layer contacts the spongy layer of the amnion and forms a
majority of chorion’s thickness. The reticular network is composed of
collagens I, III, IV, V, and VI. The basement membrane anchors the
trophoblasts to the reticular layer with collagen IV, fibronectin, and
laminin. The trophoblast layer is the deepest layer which attaches to
the decidua(48). Type I and III collagen fibres are known to provide
tissue support while type II, IV, V and VI provide scaffoldings in
maintaining tensile strength(47). Distortion in the nomenclature of
these collagen fibres diminishes the tensile strength of the
amniochorionic extracellular matrix which increases myometrial activity
and cervical remodelling leading to the onset of preterm labour(47).