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.
During pregnancy the role of the cervix shifts between two opposing functions. Throughout most of gestation, the cervix is rigid and resists tension in order to maintain the products of conception inside the uterus. At term, however, cervical function changes drastically in order to accommodate stretch and delivery. The events that control cervical function are not known. The aim of this study was to characterize changes in cervical resistance and collagen content during pregnancy in the rat. To determine the change in cervical resistance, non-pregnant and timed pregnant Sprague Dawley rats were sacrificed at various times. Their cervices were isolated and suspended in organ baths connected to a cervimeter for measurement of the stretch-tension relationship. In a different group of animals, cervical collagen content was measured using light-induced fluorescence in non-pregnant and, longitudinally, in pregnant rats. Cervical resistance and collagen content decreased progressively during pregnancy. The changes in cervical resistance mirrored those in cervical collagen content and the nadir in both occurred about two days prior to the onset of labor. Our study suggests that cervical preparation for delivery does not occur acutely at the time of labor and that cervical collagen content determines cervical resistance.
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