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).