Spontaneous Uterine Activity Research Articles

Relaxant effect of diallyl sulfide on nonpregnant rat uterus: Involvement of voltage-dependent calcium channels.

We aimed to determine the effect and mechanism of action of diallyl sulfide (DAS), an active component of sulfur-containing foods such as garlic on rat uterine activity. Isometric tension changes in longitudinal uterine strips obtained from 20 female Sprague-Dawley rats (250-300 g) in estrus stage of estrous cycle were studied in isolated organ baths containing Krebs-Henseleit solution. Diallyl sulfide (10-8 -10-6 M) caused a concentration-dependent relaxation on KCl (60 mM)-induced contractions and inhibited spontaneous peristaltic activity of uterine strips (P < 0.05). None of the following antagonists significantly changed the inhibitory effect of DAS on both KCl-precontracted uterine strips and spontaneous peristaltic activity of the uterus (P > 0.05): nitric oxide synthase inhibitor L-NAME (10-4 M), hydrogen sulfide-producing enzymes cystation β synthase and cystation γ-lyase inhibitors, aminooxyacetic acid (10-4 M) and propargylglycine (10-3 M) and nonselective cyclooxygenase inhibitor indomethacin (10-4 M). However, in calcium-free Krebs solution containing high KCl (30 mM), DAS significantly inhibited CaCl2 (10-5 -10-2 M)-induced uterine contractions in a concentration-dependent manner (P < 0.05). Diallyl sulfide has a relaxing effect on KCl-contracted rat uterus strips and an inhibitory effect on spontaneous uterine activity, possibly by decreasing the calcium influx into the cytoplasm of uterine smooth muscle cells.

Fetal Membrane Inflammation Induces Preterm Birth Via Toll-Like Receptor 2 in Mice With Chronic Gingivitis

Inflammation is associated with preterm birth. We previously described a mouse model of chronic inflammation-induced preterm birth after dental Porphyromonas gingivalis infection. The aim of this study was to employ this model system to investigate the mechanisms through which enhanced uterine contractility induces preterm birth. Messenger RNA (mRNA) encoding contraction-associated proteins, such as oxytocin receptors, was measured at various gestational time points by real-time polymerase chain reaction (PCR). Spontaneous and oxytocin-induced uterine contractile activity at gestational day 18 was assessed using a tissue organ bath. The expression levels of Toll-like receptor 2 (TLR2), TLR4, cyclooxygenase (COX)-2, nuclear factor-kappa B (NF-κB) p65, and p38 mitogen-activated protein kinase (MAPK) on gestational day 18 were also determined by real-time PCR or Western blotting. Messenger RNA encoding contraction-associated proteins was increased at gestational day 18, and the spontaneous contractile activity (1.6-fold greater area under the contraction curve) and sensitivity to oxytocin (EC50: 8.8 nM vs 2.2 nM) were enhanced in the P gingivalis group compared to those in the control group. In the P gingivalis group, COX-2 mRNA expression was not elevated in the placenta or myometrium but was upregulated 2.3-fold in the fetal membrane. The TLR2 mRNA levels in the fetal membrane were 2.7-fold higher in the P gingivalis group, whereas TLR4 levels were not elevated. Activation of the NF-κB p65 and p38 MAPK pathways was enhanced in the fetal membrane of the P gingivalis group. Thus, in mice with chronic dental P gingivalis infection, TLR2-induced inflammation in the fetal membrane leads to upregulation of uterine contractility, leading to preterm birth.

The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation

Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract.

The importance of potassium channels in the mechanism of the relaxing effect of pentoxifylline on isolated rat uteri

Background. Pentoxifylline is a methylxanthine derivative that is used to treat peripheral vascular disease. One of the mechanisms of action of pentoxifylline is the vasodilatation of blood vessels. This study examined the effect of increasing pentoxifylline concentrations on the contractility of isolated rat uteri in the presence of a potassium channel antagonist. Methods. The uteri were isolated from virgin Wistar rats (180-220 g) and suspended in an isolated organ bath chamber containing De Jalon's solution and aerated with 95% O2 and 5% CO2. The temperature was maintained at 37єC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). The preload of the preparation was approximately 1 g. The uteri were allowed to contract spontaneously or in the presence of Ca2+ (0.018 and 0.36 mM) and acetylcholine (ACh) and were treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca2+ (0.018 mM and 0,36 mM). We showed that the inhibitory effects of pentoxifylline depend on the type of muscle contractions activated and that the inhibitory effect is significantly stronger for spontaneous rhythmic activity and forin Ca2 -induced contractions of isolated rat uteri+. The relaxing effect of pentoxifylline depends on the calcium concentration in the medium. Pentoxifylline exerted the weakest relaxant effects on contractions induced by acetylcholine. In contrast to methylene blue, tetraethylammonium, or 4-aminopyridine, glibenclamide did not antagonise the relaxing effect of pentoxifylline on isolated rat uteri. Conclusion. The results obtained suggest that the mechanism of action of pentoxifylline does not lead to the opening of KATP channels. However, the opening of BKCa and voltage-dependent Ca2+ channels had some role, but to varying degrees, in the mechanism of the relaxing effect of pentoxifylline on the spontaneous rhythmic activity and calcium-induced contractions of isolated rat uteri. Our results provide additional confirmation of the dominance of the NO/cGMP signaling pathway in the mechanism of the relaxing effect of pentoxifylline (because the presence of methylene blue significantly antagonised this effect) in relation to the opening of potassium channels, especially KATP channels. These results indicate that pentoxifylline could be a potential tocolytic drug.

Abnormal fetomaternal glucocorticoid metabolism in the background of premature delivery: placental expression patterns of the 11β-hydroxysteroid dehydrogenase 2 gene

During pregnancy, 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is involved in the development of the placental barrier, and its main function is to protect the fetus from the effects of the physiological increase of maternal glucocorticoids. We compared human placental gene expression patterns of 11β-HSD2 from pregnancies that ended with preterm delivery versus full term pregnancies as controls. We used real-time PCR to assess the placental gene expression patterns of 11β-HSD2 in 104 preterm and 140 full term pregnancies (control group) at the time of delivery. In the preterm delivery group, the proportion of smokers was 26.9%, significantly higher than in the control group. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. The 11β-HSD2 gene was underexpressed in the preterm delivery group compared to normal pregnancy between 28 and 36 gestational weeks, but unchanged between 24 and 28 weeks. There was no fetal gender effect on 11β-HSD2 gene expression. The reduced activity of the 11β-HSD2 gene seen in the preterm delivery group may impair fetal defences against maternal glucocorticoid exposure. In cases of impending premature delivery, glucocorticoid effects, potentially including postnatal neurological abnormalities and growth restriction, may be worsened by prophylactic steroids given to accelerate fetal lung maturity. The impairment in fetal defences against maternal glucocorticoids due to reduced 11β-HSD2 enzyme activity appears to begin after gestational week 28.

Gene expression patterns of the Bcl‐2 and Bax genes in preterm birth

The apoptotic genes Bax and Bcl-2 are both involved in the pathogenesis of preterm delivery in conjunction with additional factors. We characterized gene expression patterns of these apoptotic regulatory genes as well as relevant environmental factors. A gene expression study with evaluation of clinical data. Semmelweis University, Budapest, Hungary. Human placental samples from 104 preterm and 140 full-term pregnancies. Gene tests were performed using real-time PCR to assess gene expression patterns of Bax and Bcl-2 in human placental samples. Clinical data were collected from our computerized database. Apoptotic gene expression pattern and clinical information against the background of preterm delivery. In placental samples from preterm delivery pregnancies, expression of the Bcl-2 gene was unchanged, whereas the Bax gene was overexpressed. Placental gene expression of Bax in preterm delivery was dependent on gestational age with gestational weeks 28-32 and 32-36 associated with overexpression, and no overexpression in gestational weeks 24-28. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. The Bax gene was overexpressed in preterm delivery, whereas expression of the Bcl-2 gene remained unchanged. After the 28(th) gestational week, apoptosis appears to be a key factor in the pathogenesis of preterm delivery.

Uterine contraction signals—Application of the linear synchronization measures

Objective In physiological research, there are not too many studies on multivariate data sets, containing two or more simultaneously recorded time series. It is important to examine synchronization in these kinds of signals. The aim of this study is to present the linear measures: the cross-correlation function, the coherence function, the wavelet cross-correlation and the wavelet coherence to assess synchronization between contractions in different topographic regions of the uterus. Study design Spontaneous uterine activity was recorded directly by a dual micro-tip catheter (Millar Instruments, Inc., USA). The device consisted of two ultra-miniature pressure sensors. One sensor was placed in the fundus, the other one in the cervix. For this analysis, a healthy patient with normal contractions, a patient with dysmenorrhea, a patient with fibromyomas in the follicular phase, and the patient with endometriosis were selected. Results For each method the values of synchronization parameters for normal contractions were higher than the values of these parameters for other pairs of signals. The differences between these four groups of the uterine contraction signals were clear. The lowest values of the synchronization measures were in the case of dysmenorrheic patient. Conclusion The analysis of synchronization of the uterine contractions signals may have a diagnostic value. For intrauterine pressure signals results obtained by means of different synchronization methods are different, but consistent.

Uterine Contractility

The analysis of the uterine contraction signals in nonpregnant states gives information about physiological changes during the menstrual cycle. Spontaneous uterine activity was recorded directly by a dual microtip catheter. The device consisted of two ultra-miniature pressure sensors. One sensor was placed in the fundus, the other in the cervix. It was important to identify time delays between contractions in two topographic locations, which may be of potential diagnostic significance in various pathologies: dysmenorrhea, endometriosis, and fecundity disorders. In this study the following synchronization measures-the cross-correlation, the semblance, the mutual information-were used to visualize the time delay changes over time. These measures were computed in a moving window with a width corresponding to approximately two or three contractions. As a result, the running synchronization functions were obtained. The running synchronization functions visualize changes in the propagation of the two simultaneously recorded signals. The propagation% parameter assessed from these functions allows for quantitative description of synchronization. Finally, we illustrate the use of running synchronization functions to investigate the effect of treatment with tamoxifen on primary dysmenorrhea.

The epidemiology of preterm labour—why have advances not equated to reduced incidence?

The major burden of preterm birth is in the developing world, where most of the increasing death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some developing countries, the growth of medical care has outstripped the growth of preventive public health, with an associated increase in iatrogenic preterm births. In developed countries, more than one-third of preterm births are medically indicated because of conditions such as fulminating pre-eclampsia or severe intrauterine growth restriction. Neither of these conditions is currently preventable. One in five preterm births is associated with multiple pregnancy, and these have been greatly increased by assisted reproduction techniques. The use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the final common pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may have adverse effects. Currently, the most promising interventions are public health related and include reducing the transmission of communicable diseases, improvements in the management of diabetes and reduction in harmful behaviours such as smoking and drug abuse.

Effects of recombinant human relaxin on pregnant rat uterine artery and myometrium in vitro

Objective: The purpose of this study was to evaluate the effects of recombinant human relaxin on the uterine artery and myometrial contractility in pregnant rats. Study Design: Uterine artery and myometrial rings from mid and term pregnant rats were used. Relaxin effect was studied on phenylephrine-induced contraction in the presence or absence of nitric oxide synthase inhibitor, Nω- nitro-l-arginine methyl ester, soluble guanylate cyclase inhibitor, 1H-oxadiazolo-quinoxaline-1-one, or adenylate cyclase inhibitor, SQ-22,536. The myometrial inhibitory effect of relaxin was studied on spontaneous and oxytocin- or protein kinase C activator-induced contractions. Results: Uterine artery relaxation by relaxin was greater at mid pregnancy compared with term. Relaxin effect was decreased by SQ-22,536, 1H-oxadiazolo-quinoxaline-1-one and Nω- nitro-l-arginine methyl ester at mid pregnancy. Relaxin inhibited spontaneous contractions at mid pregnancy but not at term. Relaxin had no effect on oxytocin- or indolactam-V-induced contractions. Conclusion: Relaxin effect is mediated by nitric oxide, soluble guanylate cyclase, and adenylate cyclase in mid pregnant uterine artery. Relaxin inhibits spontaneous uterine activity at mid pregnancy. Relaxin effect decreased at term gestation in both tissues. (Am J Obstet Gynecol 2003;188:1468-76.)

Effects of different sexual stimuli on oxytocin release, uterine activity and receptive behavior in estrous sows

This study was designed to assess effects of exogenous oxytocin (OT) on uterine activity, and to compare three different sexual stimuli in their effects on OT release, uterine activity and receptive behavior in estrous sows. Uterine activity was recorded nonsurgically, by transcervical insertion of an open-end catheter into the caudal part of the uterine lumen. After recording spontaneous uterine activity, exogenous OT was administered (Experiment 1), or one of the following stimuli was applied to the sow (Experiment 2): tactile stimuli, i.e. manual stimulation of the sow’s back and flanks, tactile stimulation in combination with boar pheromone spray (5α-androstenon), or tactile stimuli in the presence of a boar. Both exogenous OT and endogenously released OT increased uterine activity. The effect depended on the uterine activity before treatment, with the effect being greater in those sows with lower uterine activity before treatment. In Experiment 2, boar presence was the only stimulus that elicited a clear, surge-like release of OT, and also clearly increased uterine activity. Release of OT was not necessary for induction of receptive behavior: tactile stimulation alone and in combination with pheromone spray elicited a standing response in one third of the sows, but had no effect on OT release.

Myometrial activity around estrus in sows: spontaneous activity and effects of estrogens, cloprostenol, seminal plasma and clenbuterol

A new, nonsurgical, open-end catheter technique was used to study spontaneous uterine activity around estrus in sows, and the effects of estrogens, seminal plasma, cloprostenol, and clenbuterol on uterine activity. In the first experiment, uterine activity was studied in 14 multiparous, cyclic sows, during one or more estrous cycles, from day −4 to day 4 of the cycle (day 0: first day of standing estrus). From a few days before estrus until estrus, the percentage of sows showing any uterine contractions increased from 55 to 100%, and frequency and mean amplitude of uterine contractions for these sows increased from 15 to 22/h, and from 20 to 40 mmHg on average. After estrus, uterine activity decreased. There were large differences between sows in uterine activity, which were consistent over the days of the cycle. In the second experiment, 11.5 μg of estrogens in 100 ml saline ( n=17), 100 ml seminal plasma ( n=5), 1 mg cloprostenol in 100 ml saline ( n=10), 0.30 mg clenbuterol in 100 ml saline ( n=11), or 100 ml saline ( n=5) was infused IU, after recording spontaneous activity. Infusion with saline or seminal plasma did not affect uterine activity. Estrogens increased frequency of contractions. Cloprostenol increased both frequency and amplitude of contractions. Clenbuterol reduced both frequency and amplitude of contractions. In conclusion, this study shows that spontaneous uterine activity in sows is increased around estrus, and it supports the role of estrogens in boar seminal plasma in affecting uterine activity around mating. Further, this study has yielded possible tools to study the relation between uterine activity and sperm transport.

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Uterine Motility in the Cow During Puerperium

SummaryThe objective of the study was to determine uterine motility during the postpartum period in cattle. In the present study spontaneous uterine activity was recorded during postpartum period using electrodes which were surgically implanted into the myometrium 4‐6 weeks before parturition. After the placenta has been released 4‐8 hours post part, spontaneous uterine motility drastically decreased until the second week post part. The effects of oxytocin, depotocin, prostaglandin, ergometrin, detomidin on the uterine contractility, during postpartum period were investigated. Oxytocin and carbotocin given intravenously always provoked strong uterine contractions. Prostaglandin F2alpha and detomidinum HC1 stimulated uterine activity in the early puerperium. Following administration of ergometrin unequal response was recorded. Ultrasonographic examinations were performed daily with real time B‐mode scanner equipped with a 5.0 MHz linear‐array transducer (Aloka 210, Pie Medical). 10 muciparous Black‐White‐Holstein cows between 2 and 4 years old and 550‐650 kg b.w. were used. A 6‐min scan of the longitudinal view of the uterine body was recorded using video cassette recorder connected to the ultrasound scanner. A scoring system was used to determines uterine motility. Contractility scores were higher just after parturition then in the following times. Blood samples were collected daily from jugular vein for plasma progesterone and estrogen concentrations. Changes in uterine activity were associated with plasma progesterone and estrogen level.

Correlation between alpha1/beta-adrenoceptor ratio and spontaneous uterine motor activity in the post-partum rat.

The spontaneous uterine motor activity of the post-partum rat was investigated in parallel with the in-vitro determination of the density of the alpha1 and beta-adrenergic receptors of the myometrium. The in-vivo experiments were performed by an improved method, using a Millar catheter fitted with a latex microballoon. The spontaneous contractility of the post-partum rat uterus was found to be highest 24 h after delivery, indicating that this time is the most suitable for pharmacological examinations of tocolytic agents. A very close correlation was found between the results of the in-vivo experiments and the alpha1/beta-adrenergic receptor ratio assessed by an in-vitro receptor assay, thus indicating that the state of the adrenergic receptor system fundamentally determines the contractility of the uterus. This conclusion is supported by the fact that the pharmacological sensitivity of the rat uterus to prazosin and fenoterol changed as a function of the post-partum time in accordance with the alpha1/beta-adrenoceptor ratio. These results and the relevant data available reveal a crucially important role of an alpha1-adrenoceptor-mediated process, implicating alpha1-blockers as theoretically potent agents for inhibition of premature uterine contractions.

Fibromyomas and uterine contractions.

Women with uterine fibromyomas may suffer from dysmenorrhea, menorrhagia or infertility, which all may be due to an effect of the fibroids on uterine activity. The effect of myomectomy on uterine contractility is unknown. In women undergoing myomectomy because of dysmenorrhea, menorrhagia or infertility, intrauterine pressure was recorded before and three months after the operation on corresponding days of the menstrual cycle. Records were obtained during spontaneous uterine activity as well as after oxytocin and vasopressin challenge by intravenous bolus injections of 10 pmol/kg body weight. The area under the recording curve (AUC), maximal amplitude of uterine contractions and deformation index of uterine pressure recordings were measured. In six women, in whom recordings could be obtained before and after operation on corresponding days of late follicular phase of the menstrual cycle, the AUC and maximal amplitude of contractions increased after myomectomy. The effect of oxytocin injection also varied, whereas no difference was seen in effect of vasopressin. It is suggested that women with uterine fibromyomas may have disturbed uterine spontaneous contractions and responsiveness, which may be regulated by myomectomy.

Spontaneous uterine activity during the oestrous cycle of the camel ( Camelus dromedarius)

Spontaneous uterine activity was studied in three cyclical female camels implanted with balloon-tipped catheters connected to pressure transducers. Another camel was not operated upon. The frequency of contractions in both horns varied from zero to a maximum of 90 h −1, whereas the amplitude of contractions varied from zero to a maximum of 3.5 kPa during the experimental period. Uterine activity was higher in the left horn. Concentrations of oestradiol-17β increased as the follicle grew in size in the non-operated camel. The pattern of uterine activity was correlated with the circulating levels of oestradiol-17β ( r=0.83, P<0.001, n=3). It was concluded that uterine activity in the camel is dependent on oestrogen level.

Effects of methoxamine on spontaneous uterine activity and blood flow of the rat uterus 'in vivo'.

The vascular (blood pressure, heart rate and peripheral blood flow) and uterine (spontaneous motility) responses to intravenous methoxamine were studied in anaesthetized rats pre-treated with diethylstilboestrol. Methoxamine produced an increase (0.5-2 mg/kg) or did not modify (0.01 and 3 mg/kg) spontaneous uterine motility. The alpha 1-agonist also induced a hypertensive effect (0.1-3 mg/kg) accompanied by bradycardia at the highest doses, and a decrease in blood flow significantly greater in intestinal than uterine tissues. These effects were abolished by prazosin. The uterine action of methoxamine in vivo appears to result from the balance between myometrial alpha 1-excitatory effect and vascular alpha 1-vasoconstriction which induced uterine inhibition. The oestrogens appear to protect the alpha 1-mediated vasoconstriction.

Studies of the spontaneous motility and the effect of histamine on isolated myometrial strips of the nonpregnant human uterus: The influence of various uterine abnormalities

We investigated the spontaneous uterine activity of isolated corpus uteri myometrial strips from 30 patients with nonpathologic myometrium, 26 patients with uterine myoma, 23 patients with uterine adenomyosis, and three patients with uterine malignancy. We also investigated the influence of these conditions on the response of the uterus to histamine. The results show the same qualitative cyclic changes of the spontaneous motility of isolated myometrial strips throughout the menstrual cycle in all the abnormalities studied. These changes are characterized by a low amplitude and high frequency of spontaneous contractions in the proliferative phase and lower frequency with higher amplitude of contractions in the secretory phase. The isolated strips from patients with myomas present the highest spontaneous activity in reproductive age and preclimacteric women, but not in menopausal women. Histamine produced concentration-related contractions that are not significantly different in all the myometrial strips studied.

The influence of lead ions on uterine activity in the rat

Spontaneous uterine activity and reactivity to oxytocin, naproxen and PGF 2α were studied in vitro in 80 rats, which for 2–8 weeks had been exposed to different concentrations and combinations of Pb 2+, Zn 2+ and Cu 2+ in their water supply or had been given clean water for control. In rats given only Pb 2+ in concentrations of 1000 and 500 ppm for 6 weeks the uterine activity was significantly increased, whereas in groups given the other ions alone, or Pb 2+ for 6 weeks followed by 2 weeks of clean water or Zn 2+ or Cu 2+ no change was observed. The responses to the oxytocin, naproxen and PGF 2α did not differ. These results suggest that contamination with lead ions might be one of the etiological factors involved in conditions with increased uterine activity.