Control and assessment of the uterus and cervix during pregnancy and labour

Abstract

Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.

Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

“…The dramatic increase in cervical volume during pregnancy, due mainly to oedema formation, widespread reorganization of collagen fibres and fibroblastic cell proliferation (Sherwood 1994, Garfield et al 1998, Leppert 1998, could explain the absence of differences in relative vascular area during gestation. However, during the second half of pregnancy, the absolute vascular area of the uterine cervix exhibited a sustained increment, reaching higher values around parturition.…”

“…Previous studies have suggested that nitric oxide (NO) is an important local mediator in the uterus and cervix during pregnancy and parturition (Garfield et al 1998). NO production in the cervix is low during gestation and becomes upregulated once pregnancy advances to term (Maul et al 2003).…”

Identification of term and preterm labor in rats using artificial neural networks on uterine electromyography signals

“…EMG parameters are thought to indicate how well prepared the uterus is for labor (8)(9)(10). The significant difference in uterine EMG parameters after ANN classification is an indirect measure of the ability of the ANN classification method to detect the important changes and numerical relationships of the uterine parameters which are indicative of labor.…”

“…For example, previous EMG experiments established that the electrical activity of the myometrium is actually responsible for myometrial contractions (3)(4)(5). Furthermore, extensive studies have been done in the last 60 years to monitor uterine contractility using the electrical activity measured from electrodes placed on the uterus (6,7), or on the abdominal surface (8)(9)(10).…”

Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats

“…Progesterone also supports uterine quiescence by up-regulation of pathways associated with relaxation like the nitric oxide system , which promotes synthesis of intracellular cyclic guanosine 3 0 ,5 0 -monophosphate (GMP; Buhimschi et al 1995). Finally, progesterone also inhibits production of uterotonins like prostaglandin F2a (PGF2a; Garfield et al 1998, Farina et al 2004.…”