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The effect of estrogen, progesterone and prostaglandin F2 alpha on uterine contractions in seasonally anovulatory mares.

Uterine contractions were studied in two experiments utilizing ultrasonography and seasonally anovulatory mares. A one-minute ultrasound scan was done to produce longitudinal real-time images of the uterine body and an overall uterine contractile activity score (0 = no or minimal activity to 4 = maximal activity) was assigned to each scan. In experiment 1, a two-hour uterine activity trial (one score every 10 minutes) was done in mares given a single injection of prostaglandin F2 alpha (PGF2 alpha group; n = 4) and in control mares (n = 4). There was no difference between the two groups over the two-hour trial (mean activity score averaged over the two-hour trial: PGF2 alpha group, 0.2; control group, 0.1). In experiment 2, 16 mares were randomly assigned to one of four groups: 1) controls (corn oil vehicle), 2) 1 mg estradiol 17 beta on days 0 to 9 and 100 mg progesterone on days 10 to 20 (E2--greater than P4 group), 3) 100 mg progesterone on days 0 to 20 (P4 group), and 4) 100 mg progesterone on days 0 to 9 and 1 mg estradiol 17 beta + 100 mg progesterone on days 10 to 20 (P4--greater than E2 + P4 group). Uterine activity was assessed for each mare daily. The day by group interaction was significant. Scores for the E2--greater than P4 group were greater on days 4 to 11 (P less than .05) than for the other three groups. From day 14 to 21, scores did not differ among the three steroid-treated groups (except on day 15), but the scores averaged over each steroid-treated group were greater for each day (P less than .1 or .05) than for the controls (except on day 17).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fetal vascular pressure responses to nonlabor uterine contractions: dependence on amniotic fluid volume in the ovine fetus.

OBJECTIVE: This investigation tested the hypothesis that elevations in fetal vascular pressures during nonlabor uterine contractions would be eliminated during polyhydramnios and augmented during oligohydramnios. STUDY DESIGN: Twenty-two chronically catheterized fetal sheep were divided into three groups: (1) control with normal amniotic fluid volume, (2) polyhydramnios produced by amnioinfusion, and (3) oligohydramnios produced by fluid drainage. Fetal arterial pressure, venous pressure, and amniotic fluid pressure were continuously recorded with on-line computer techniques. Amniotic fluid pressure was continuously subtracted from fetal arterial pressure and fetal venous pressure to correct to the fetal zero pressure reference. One minute averages were collected for 30 minutes centered around the nonlabor uterine contraction. RESULTS: Amniotic fluid pressure increased significantly during nonlabor uterine contractions in the control group. During polyhydramnios the amplitude and duration of the amniotic fluid pressure elevation were similar to those of controls (not significant). During oligohydramnios the duration of the uterine contractions was similar to that of both controls and polyhydramnios groups; however, the amplitude was less (p < 0.001). Fetal vascular pressures increased significantly during nonlabor uterine contractions in the control group (p < 0.001) but did not change significantly during nonlabor contractions in the polyhydramnios group. The contraction-induced elevations in fetal arterial pressure and fetal venous pressure in the oligohydramnios group were significantly greater than those in the control group (p < 0.001). CONCLUSION: This study shows that the fetal vascular pressure responses to nonlabor uterine contractions were modified significantly by increases or decreases in amniotic fluid volume. The fact that the fetal arterial pressure and fetal venous pressure responses were augmented during oligohydramnios and eliminated during polyhydramnios suggests that direct compression or a conformational change of the fetus may be the cause of the vascular pressure changes during nonlabor contractions.

Amniotic Fluid↗

Human fetal membranes inhibit spontaneous uterine contractions.

Fetal membranes are postulated to play a role in paracrine signaling during the initiation of labor in women. We developed a dual chamber-fetal membrane-uterine muscle model to study the effect of human fetal membranes on spontaneous uterine contractions. In this model, full-thickness fetal membranes (amnion, chorion, and maternal decidua) are sealed into a Plexiglass chamber. The membranes partition the chamber into a maternal and fetal compartment. Chorion and decidua face the maternal side, and amnion faces the fetal side. An estrogenized rat uterine muscle strip is anchored into the maternal side as a bioassay to measure effects of fetal membranes on uterine contractions. Fetal membranes cause a 40% decrease in uterine contractions compared to basal condition (no membranes). Inhibition is reversible after removal of the membranes. The inhibition is specific to the chorion/decidual side because reversal of membranes with amnion toward the muscle did not show inhibition. Uterine contractions did not change over time in control chambers in which Parafilm substituted for membranes. A model for studying paracrine regulation of uterine contractions by human fetal membranes has been developed. The model provides evidence that fetal membranes inhibit uterine contractions. This inhibitory effect may contribute to uterine quiescence during pregnancy.

Animals↗

What have we learned about uterine contractions and preterm birth? The HUAM Prediction Study.

Measurement of uterine contraction frequency has been employed as a screening test to identify women with increased risk of preterm birth, and as an aid in the early diagnosis of preterm labor. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed a prospective, blinded observational study of uterine contraction frequency to detect and predict preterm labor and birth, respectively. The goal of the study was to assess the sensitivity, specificity, and positive and negative predictive value of various measures of uterine contraction frequency. Data collected from 306 women revealed that contraction frequency was significantly greater in women who would ultimately deliver before rather than after 35 weeks' gestation. However, both sensitivity and positive predictive value of any measure of contraction frequency to predict preterm birth were poor. Contraction frequency did not increase significantly within 1 or 2 weeks of an episode of preterm labor. These results serve to explain the absence of an association between contraction-based surveillance and preterm birth in randomized trials conducted in women at risk of preterm birth.

Female↗

[Uterine contraction. Mechanism, regulation and pharmacology].

Uterine contraction is essential for genital tract functioning among mammal females. For women, the main interest are the possible alterations, and the ability to manage them with drug use. Due to the fact that contraction regulation is multifactorial, several medications are used in basic and clinical research, both to know contraction mechanisms, and to interfere with its alterations. This review considers contraction mechanism at molecular-cellular level, and the different molecules regulating it; as well as the effects that different medications produce upon such mechanism.

Angiotensin II↗

Catecholamines are not linked to myometrial phospholipase C and uterine contraction in late pregnant and parturient mouse.

1. We investigated whether catecholamines through activation of alpha(1)-adrenergic receptors (alpha(1)-AR) are involved in mouse uterine contraction at parturition. Myometrial phospholipase C (PLC) activity and uterine contraction were measured in response to noradrenaline (NA), the specific alpha(1)-AR agonist phenylephrine (Phe) and oxytocin (OT). 2. Using the reverse transcription-polymerase chain reaction RT-PCR, we detected the alpha(1a)-AR subtype in late pregnant mouse myometrium. We also detected, by immunoblotting studies, PLCbeta(1), PLCbeta(3) and different alpha-subunits of pertussis toxin-insensitive (Galpha(q/11)) and -sensitive G proteins (Galpha(o/i3), Galpha(i1/2)). 3. Phenylephrine and NA did not alter the myometrial inositol phosphate (InsP) production of late pregnant or parturient mouse. In similar conditions, OT increased InsP production in a dose-dependent manner. Consistent with these results, only OT (10 microM) recruited PLCbeta(1) and PLCbeta(3) to myometrial plasma membranes. The OT-induced InsP response was not altered by pertussis toxin (300 ng ml(-1), 2 h pretreatment), suggesting the involvement of a member of the Galpha(q) family. 4. Noradrenaline and Phe failed to increase uterine contraction at late pregnancy and at parturition. In contrast, OT induced uterine contraction in a dose-dependent manner with maximal increase (400 %) at a concentration of 1 microM. 5. The results indicate that OT receptors (OTR) but not alpha(1)-AR are linked to myometrial PLC activation and uterine contraction in late pregnant and parturient mouse. This discrepancy between mouse and other mammals could be attributed to the alpha(1)-AR subtype expressed in myometrium at this time.

Adrenergic beta-Antagonists↗

The effects in the rat of two fragments of parathyroid hormone-related protein on uterine contractions in situ.

Synthetic parathyroid hormone fragment PTH(1-34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone-related protein fragment PTHrP(1-34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine-stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75-86 amide) (10(-9)-10(-7) M) was without effect, synthetic hPTHrP(1-34) (10(-9)-10(-7) M) was capable of inhibiting, in a dose-related fashion, uterine muscle contractions precontracted with 10(-6) M-acetylcholine. In a second series of experiments the bovine PTH(3-34) fragment itself was shown to have no stimulatory effect on acetylcholine-stimulated contractions. Also this fragment in an equimolar concentration (10(-7) M) failed to antagonize the effects of PTHrP(1-34) on acetylcholine-stimulated uterine contractions. However, a 100-fold excess molar concentration of bPTH(3-34) (10(-6) M) completely abolished the inhibitory action of hPTHrP(1-34) (10(-8) M) on acetylcholine-stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1-34) and PTHrP(1-34) on uterine contractions depends on the integrity of the amino-terminal region of the molecule.

Acetylcholine↗

A computer model of uterine contractions based on discrete contractile elements.

OBJECTIVE: To predict uterine contraction waveforms using a microcomputer-based model of uterine activity based on discrete contractile elements, varying the shape of the model, total number of cells, and pacemaker locations. METHODS: The model is a hollow ovoid composed of discrete contractile elements (cells) that propagate electrical impulses, generate tension, and have defined contracting and refractory periods. Each cell contacts eight surrounding cells and propagates impulses iteratively from cell to cell. Contraction pressure is the sum of the tension contributions by contracting cells. Sample contraction waveforms were generated based on various numbers of cells organized in ovoids with long:short axis ratios of 1:1, 3:2, and 2:1, with one or two pacemakers at varying positions. RESULTS: Contraction waveforms are altered by altering the shape of the matrix, but not by increasing the number of contractile elements. The vertical placement of the pacemaker has a dramatic effect on the shape and symmetry of contractions, including the development of patterns characteristic of "dysfunctional" uterine contractions. CONCLUSION: Abnormal uterine contraction patterns may result from pacemaker activity in unusual locations, such as mid-uterus. Further refinement of this computer model of uterine activity may contribute to a better understanding of the genesis of normal and abnormal intrauterine pressure waveforms and their relationship to the progress of labor.

Computer Simulation↗

Uterine contractions increase fetal heart preload.

OBJECTIVE: The preload index (PLI) has been shown to increase in the recipient fetus of twin-twin transfusion syndrome in the presence of uterine contractions. The objective of this study was to determine whether there are changes in PLI in the presence of uterine contractions in normal fetuses. METHODS: Inferior vena cava blood flow was measured using Doppler sonography in 45 normal fetuses at 18-41 weeks' gestation in the presence of uterine contractions and during quiescence and the PLI was compared between groups. RESULTS: There was a highly significant difference (P < 0.0001) between the mean +/- SD PLI in fetuses in the absence (0.235 +/- 0.07) and in the presence (0.534 +/- 0.183) of uterine contractions. CONCLUSION: Uterine contractions appear to increase fetal preload conditions in normal pregnancy.

Blood Flow Velocity↗

Effect of benzyl isothiocyanate on spontaneous and induced force of rat uterine contraction.

The present study examines the effect of benzyl isothiocyanate (BITC) on uterine contraction in vitro. BITC (10-320 microM) caused irreversible, concentration-dependent inhibition of the spontaneous, prostaglandin F(2alpha) (PGF(2alpha)) and oxytocin-induced force of gravid and non-gravid rat uterine contractions in contrast to equivalent concentrations of DMSO (solvent control). At 160 microM of BITC, spontaneous, PGF(2alpha) and oxytocin-induced force of gravid rat myometrial contractions were reduced to 16 +/- 6%, 15 +/- 7 % and 17 +/- 4% (of the control contractions), respectively. Moreover, at 320 microM of BITC, spontaneous, PGF(2alpha) and oxytocin-induced force of non-gravid rat uterine contractions were reduced to 10+/-5 %, 4+/-1 % and 7+/-2 % (of the control contractions), respectively. Incubation of isolated non-gravid rat uterine strips in Ringer Locke solution containing 100 microM of BITC for 1h prior to recording their activity also caused significant and irreversible depression of KCl (60mM)-induced tension development in the uterus relative to the solvent control (P < 0.01). In 56% of BITC-pretreated uterine tissues, spontaneous contractions were totally abolished. Cryosections of BITC-treated uterus (hematoxyline and eosin stained) examined under light microscope revealed structural disintegrity with marked vacuolar degeneration of the endometrium and myometrium. It thus appears that like the vascular smooth muscle (reported by previous workers), BITC is also capable of causing functional aberration of isolated uterus by provoking degeneration of the myometrium.

Animals↗

Sonographic assessment of the cervix before, during and after a uterine contraction is effective in predicting the course of labor.

OBJECTIVE: To investigate whether the degree of change in cervical length during a uterine contraction is predictive of subsequent progression of labor. METHODS: The subjects were 73 uncomplicated parturient women at term. We observed the cervix before, during and after a uterine contraction by transvaginal ultrasound in the first stage of labor and determined the degree of cervical shortening during the contraction relative to the cervical length before contraction. We related the degree of cervical shortening to labor patterns at the time of the ultrasound examination, which were retrospectively determined by reviewing the partogram. RESULTS: The cervix was shortened in length by about 50% on average during a uterine contraction in the normal course of labor. The degree of cervical shortening was significantly greater in the normal latent and active phases than it was in the prolonged latent phase, protracted active phase and false labor, whereas there were no differences between the former two phases nor between the latter three phases. Nulliparous and parous women exhibited almost the same degree of shortening in the normal latent and active phases. CONCLUSIONS: Real-time ultrasound observation of the cervix during uterine contraction could help differentiate inefficient uterine contractions from normal ones and thus predict the subsequent course of labor.

Adolescent↗

Long-term observations of uterine contractions in nonpregnant dogs.

Uterine contractile activity in nonpregnant conscious dogs was investigated based on 2- to 6-mo-long continuous recording by means of a chronically implanted force transducer. We found that nonpregnant uterine contractile activity could be classified into six major patterns: sporadic contractions, weak and strong tonic contractions, weak and strong phasic contractions, and phasic contraction bursts. The contractile patterns during proestrus and estrus were the most active, with strong phasic and tonic contractions and phasic contraction bursts. The phasic and tonic contractions were inhibited dose-dependently by a beta 2 adrenergic agonist, ritodrine, and reproduced by an alpha 2 adrenergic agonist, clonidine. In contrast, the cholinergic inhibitors atropine and hexamethonium did not affect the spontaneous occurrence of these contractions, although bethanechol evoked uterine contractions. Oxytocin and prostaglandin F2 alpha-induced contractions were phasic during estrus, whereas they showed tonic increases with phasic contractions during proestrus, diestrus, and anestrus, and these contractions did not resemble the spontaneous contractions. In conclusion, the nonpregnant uterus contracts continuously in harmony with the estrous cycle phases, and its contractile activity is enhanced by alpha adrenergic receptors and inhibited by beta 2 adrenergic receptors.

Adrenergic Agonists↗

[Effect of estrone on rat uterine contraction induced by prostaglandin (author's transl)].

Influence of estrone on uterine contraction and increase of internal pressure of uterus induced by PG were studied in the rat. The sensitivity of the uterus to PG was increased after estrone injection, the maximum effect being observed 72 hours after the administration. Regarding uterine contraction and increase of internal pressure induced by PGE2 or PGF2alpha, the amplitude was enlarged but the frequency was decreased with estrone injection. Contraction and increase of internal pressure induced by PG were well correlated in the rat uterus treated with estrone. Progesterone inhibited the stimulatory action of estrone on uterine contraction induced by PG. These results suggest that estrone may play an important role in action of PG in rat uterus.

Animals↗

Direct effect of parathyroid hormone on rat uterine contraction.

Synthetic bovine parathyroid hormone containing the 1-34 NH2 terminal amino acids [bPTH-(1-34)] is capable of inhibiting stimulated uterine contraction. The purpose of the present investigation is to determine whether the inhibitory action of bPTH-(1-34) is a direct action of the hormone fragment. The effect of different synthetic preparations of bPTH-(1-34), salmon calcitonin, corticotropin-inhibiting peptide and bovine serum albumin on oxytocin-stimulated uterine contraction was determined. In addition, the effects of atropine, propranolol, phentolamine, pyrilamine, cimetidine and the prostaglandin synthetase inhibitor indomethacin on the inhibitory action of bPTH-(1-34) on uterine contraction was determined. Both synthetic preparations of bPTH-(1-34) inhibited oxytocin-initiated contractions similarly. Salmon calcitonin, corticotropin-inhibiting peptide, and bovine serum albumin did not alter oxytocin-stimulated uterine contractions. The salmon calcitonin also did not alter the ability of bPTH-(1-34) to exert its inhibitory effect on uterine contraction. Cholinergic, alpha and beta adrenergic, histaminergic (H1 and H2) and prostaglandin synthetase inhibitors did not alter the action of bPTH-(1-34). These results suggest that the action of bPTH-(1-34) is 1) not due to the presence of a contaminant in the synthetic hormone preparation and 2) that the effect could be due to a direct action effect of the hormone fragment on uterine tissue.

Adrenocorticotropic Hormone↗

Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats.

The present study was designed to investigate the possible modulator effect of melatonin on uterine estrogen and progesterone receptors in rats as well as the uterine response to oxytocin. Non-pregnant rats were pretreated with melatonin in a dose of 0.8 mg kg(-1) per day for 15 consecutive days. Control animals received the vehicle. The uterus was dissected out and uterine contraction in one horne was recorded in vitro for each animal as a response to oxytocin (0.5 x 10(-11) to 2 x 10(-11)M). The other uterine horne was subjected to estrogen and progesterone receptors detection by immunohistochemical and image analysis techniques. The results reveal a significant reduction (59%) in the number of uterine estrogen receptors with concomitant increase in the progesterone receptors (53%) in melatonin-pretreated rats as compared to the control ones. In addition, our data show an inhibitory effect of melatonin on the uterine contraction as a response to oxytocin (0.5 x 10(-11), 1 x 10(-11), and 2 x 10(-11)M) amounting to 48, 77, and 59.5% reduction, respectively, in the amplitude of contraction as well as 62, 19.9, and 47% reduction in the area under the curve (AUC) of uterine contractions, respectively. The data, so far obtained, may indicate a possible relationship of melatonin-induced modulation of the number of estrogen and progesterone receptors and its inhibitory effect on uterine contraction. These findings merit further investigations on the possible beneficial role of melatonin in a plethora of hormone-dependent uterine disorders.

Animals↗

Frequency of uterine contractions and the risk of spontaneous preterm delivery.

BACKGROUND: The measurement of the frequency of uterine contractions has not been useful for reducing the rate of preterm delivery in randomized trials. Nonetheless, ambulatory monitoring of contractions continues to be used in clinical practice. METHODS: We assessed the frequency of uterine contractions as a predictor of the risk of spontaneous preterm delivery before 35 weeks of gestation. We enrolled women with singleton pregnancies between 22 and 24 weeks of gestation. The women used a contraction monitor at home to record contraction frequency twice daily on 2 or more days per week from enrollment to delivery or 37 weeks of gestation. RESULTS: We obtained 34,908 hours of successful monitoring recordings from 306 women. Although more contractions were recorded from women who delivered before 35 weeks than from women who delivered at 35 weeks or later, we could identify no threshold frequency that effectively identified women who delivered preterm infants. The sensitivity and positive predictive value of a maximal hourly frequency of contractions of four or more between 4 p.m. and 3:59 a.m. were 9 percent and 25 percent, respectively, at 22 to 24 weeks and 28 percent and 23 percent at 27 to 28 weeks. Other proposed screening tests, such as digital and ultrasound evaluations of the cervix and assays for fetal fibronectin in cervicovaginal secretions, also had low sensitivity and positive predictive value for preterm labor. CONCLUSIONS: Although the likelihood of preterm delivery increases with an increased frequency of uterine contractions, measurement of this frequency is not clinically useful for predicting preterm delivery.

Cervix Uteri↗

Excessive uterine contractions: effect on the incidence of preterm delivery in twin gestation.

OBJECTIVE: To evaluate the effect of uterine contractions on the incidence of preterm delivery within 7 and 14 days in twin pregnancies. STUDY DESIGN: Study patients were identified from a large database composed of women receiving outpatient surveillance with home uterine contraction monitoring. We included tracings collected on a routine or acute basis from twin pregnancies without cerclage at 24.0-36.0 weeks. Tracings from patients with indicated delivery were excluded. Fisher's exact and Pearson's X2 tests were used. RESULTS: Datafrom 2,423 patients who recorded 8,291 acute tracings and 12,649 routine tracings were analyzed. Preterm delivery within 7 days followed 1.4% of routine vs. 6.6% of acute tracings (p < 0.001). Preterm delivery within 14 days followed 5.1% of routine vs. 16.8% of acute tracings (p < 0.001). CONCLUSION: Preterm uterine contractions affect pregnancy prolongation and outcome in twin pregnancies utilizing outpatient surveillance. Evaluation of patients exhibiting elevated preterm uterine contractions is warranted.

Adult↗

[Uterine contraction induced by carbachol is inhibited by melatonin].

It has been suggested that the pineal gland has a specific role in the regulation of reproductive functions. Melatonin, secreted by pineal gland, is involved in the control of mammalian reproduction. Previous investigations have show that melatonin reduced the smooth muscle contraction. The purpose of the present study was to investigate the effect of melatonin on the uterine contraction provoked by carbachol. This effect was studied in isolated uterus were taken from Wistar rats pretreated with diethylstilboestrol. Here, we describe the effects of various concentrations of melatonin was found to inhibit the carbachol-induced uterine contraction. Our results show that CE50 of carbachol increment in present to 10(-9) and 10(-6) M/ml of melatonin. The degree of the inhibitory effect of melatonin to concentration of 10(-9) M/ml is most evident that 10(-6) M/ml. Thus, it is concluded that melatonin has an pharmacological inhibition effect on the contraction uterine provoked by carbachol, act as physiological antagonist.

Animals↗