Oxytocin-induced Contractions Research Articles

Preserved Oxytocin-Induced Myometrium Contraction and Sensitivity to Progesterone Inhibition Following Rat Uterus Thermal Insult. Impact on Fertility

Preserved Oxytocin-Induced Myometrium Contraction and Sensitivity to Progesterone Inhibition Following Rat Uterus Thermal Insult. Impact on Fertility

Role of the Adenylate Cyclase/Cyclic AMP Pathway in Oxytocin-Induced Lacrimal Gland Myoepithelial Cells Contraction

Role of the Adenylate Cyclase/Cyclic AMP Pathway in Oxytocin-Induced Lacrimal Gland Myoepithelial Cells Contraction

Role of the Phospholipase C Pathway and Calcium Mobilization in Oxytocin-Induced Contraction of Lacrimal Gland Myoepithelial Cells.

PurposeWe reported that oxytocin (OXT), added to freshly prepared lacrimal gland lobules, induced myoepithelial cell (MEC) contraction. In other systems, OXT activates phospholipase C (PLC) generating Inositol 1,4,5-trisphosphate (IP3) which increases intracellular calcium concentration ([Ca2+]i) causing contraction. The aim of the current study was to investigate the role of this pathway in OXT-induced contraction of MEC.MethodsTear volume was measured using the cotton thread method. Lacrimal gland MEC were isolated and propagated from α-smooth muscle actin (SMA)-green fluorescent protein (GFP) mice, in which MEC express GFP making them easily identifiable. RNA and protein samples were prepared for RT-PCR and Western blotting for G protein expression. Changes in [Ca2+]i were measured in Fura-2 loaded MEC using a ratio imaging system. MEC contraction was monitored in real time and changes in cell size were quantified using ImageJ software.ResultsOXT applied either topically to surgically exposed lacrimal glands or delivered subcutaneously resulted in increased tear volume. OXT stimulated lacrimal gland MEC contraction in a dose-dependent manner, with a maximum response at 10−7 M. MEC express the PLC coupling G proteins, Gαq and Gα11, and their activation by OXT resulted in a concentration-dependent increase in [Ca2+]i with a maximum response at 10−6 M. Furthermore, the activation of the IP3 receptor to increase [Ca2+]i is crucial for OXT-induced MEC contraction since blocking the IP3 receptor with 2-APB completely abrogated this response.ConclusionsWe conclude that OXT uses the PLC/Ca2+ pathway to stimulate MEC contraction and increase lacrimal gland secretion.

Investigation of Effects of Gadolinium-Based Contrast Agents on Uterine Contractility Using Isolated Rat Myometrium.

Despite concerns about safety, gadolinium-based contrast agents (GBCAs) are still used for abdominal and pelvic imaging during pregnancy. Researchers have mainly focused on teratogenicity, while very little is known about their possible direct effects on uterine contractility, yet free gadolinium potentially impacts contractility through interaction with calcium channels. To investigate possible effects of selected GBCAs (namely gadoteridol, gadoversetamide, gadobutrol, gadoterate meglumine, and gadoxetic acid) on the contractility of rat myometrium. In vitro organ bath study. Myometria were isolated from adult (10-12 weeks old) Sprague Dawley rats, both pregnant (N=8) and nonpregnant (N=36). NA. Myometrial strips were suspended in tissue bath containing physiological saline and isometric contractions were recorded. GBCAs were added to the tissue bath cumulatively, and their effects on contractility parameters (quantified by amplitude, frequency, and area under contractility curve [AUC]) were evaluated by 10-minute intervals. Normality data, checked by Shapiro-Wilk test, were transformed by arcsine when needed. One- or two-way analysis of variance was performed, where appropriate, followed by Student-Newman-Keuls test. A P value of <0.05 was considered statistically significant. All of the assayed GBCAs elicited some alterations in the myometrial contractility in a concentration-dependent manner. Gadoterate meglumine, gadoxetic acid, and gadoversetamide caused a concentration-dependent significant attenuation in AUC (oxytocin-induced, from 100% during control period to 45.1 ± 9.0% (nonpregnant) and 59.9 ± 8.5% (pregnant), for 90 μM gadoterate meglumine; respectively), and frequency of the spontaneous and oxytocin-induced contractions. Gadobutrol and gadoteridol at highest dose significantly attenuated mean AUC and frequency of oxytocin-induced contractions of nonpregnant myometrium. Results from this in vitro study indicate that GBCAs elicit modulation of myometrial contractions at clinically relevant concentrations. These effects may account, at least partially, for the known potential side effects (rare cases of miscarriages and elective abortion) of these agents. 1 TECHNICAL EFFICACY: Stage 5.

The Effect of Morbid Obesity or Advanced Maternal Age on Oxytocin-induced Myometrial Contractions: An In Vitro Study

(Can J Anesth. 2020;67:836–846) Worldwide, the rate of pregnant women who are of advanced maternal age (AMA) or who are overweight or morbidly obese is rising. These factors are associated with higher rates of labor induction or augmentation, prolonged labor, cesarean delivery and postpartum hemorrhage (PPH). Oxytocin is used both to prevent and treat PPH and for labor induction and augmentation. However, when oxytocin use is prolonged, a phenomenon known as oxytocin receptor desensitization can occur. This desensitization weakens the contractile response to repeated oxytocin treatment and can lead to severe PPH. The aim of this study was to investigate in vitro the effect of oxytocin on myometrial contractions in pregnant women with AMA and morbid obesity.

Conflicting Nongenomic Effects of Progesterone in the Myometrium of Pregnant Rats.

Recently, it has been suggested that progesterone affects the contractile activity of pregnant myometrium via nongenomic pathways; therefore, we aimed to clarify whether progesterone causes and/or inhibits pregnant myometrial contractions via nongenomic pathways. Our in vitro experiments using myometrial strips obtained from rats at 20 days of gestation revealed that progesterone caused myometrial contractions in a concentration- and time-dependent manner at concentrations up to 5 × 10−7 M; however, this effect decreased at concentrations higher than 5 × 10−5 M. Similarly, progesterone enhanced oxytocin-induced contractions up to 5 × 10−7 M and inhibited contractions at concentrations higher than 5 × 10−5 M. Conversely, progesterone did not enhance high-KCl-induced contractions but inhibited contractions in a concentration- and time-dependent manner at concentrations higher than 5 × 10−7 M. We also found that RU486 did not affect progesterone-induced contractions or the progesterone-induced inhibition of high-KCl-induced contractions; however, progesterone-induced contractions were blocked by calcium-free phosphate saline solution, verapamil, and nifedipine. In addition, FPL64176, an activator of L-type voltage-dependent calcium channels, enhanced high-KCl-induced contractions and rescued the decrease in high-KCl-induced contractions caused by progesterone. Together, these results suggest that progesterone exerts conflicting nongenomic effects on the contractions of pregnant myometrium via putative L-type voltage-dependent calcium channels.

Analysis of decay kinetics of the cytosolic calcium transient induced by oxytocin in rat myometrium smooth muscle cells.

The method of kinetic analysis of the relaxation phase of the mechanical response of the smooth muscle previously proposed by Burdyga and Kosterin was applied to study the dynamics of the decay of oxytocin-induced calcium transients in cytosol of the rat myometrium smooth muscle cell detected by a fluorescence signal generated by a calcium-sensitive probe fluo-4 using a laser scanning confocal microscope. The experimental data were well linearized in the coordinates ln [(Fm - F)/F] vs lnt (F and Fm are the current fluorescence intensity of the calcium probe and the fluorescence intensity at the maximum of the calcium transient, respectively, while t is the time). The empirical parameters n and τ were determined by which the maximal normalized relaxation rate Vn was calculated for five different ROIs (regions of interest) in the myocyte cytosol. It proved to be almost the same for all ROIs. The maximal normalized relaxation rate calculated from the fluorescence intensity was always lower than that calculated from the corresponding calcium concentration, i.e. the cytosolic Ca2+ concentration in the relaxation phase decreases faster than the corresponding fluorescence intensity. The value of the maximal normalized relaxation rate calculated both from the fluorescence intensity and from the force of oxytocin-induced contractions of isolated rat uterus longitudinal smooth muscles (according to Tsymbalyuk and Kosterin) was exactly the same. This indicates that in the relaxation phase, the decreasing curves of both the fluorescence intensity and the contraction forces coincide.

41In vitro human myometrial contractility in pregnancies complicated with obesity

The onset of parturition in pregnant women with obesity is frequently delayed. Without induction, these women are nearly twice as likely as normal-weight women to have prolonged pregnancies. Obesity has been shown to be an independent risk factor for cesarean birth, even after controlling for birth weight. It has been suggested that myometrial contractility is impaired in women with obesity. In this study we aimed to investigate whether contractility is truly reduced in women with obesity compared to their normal-weight counterparts utilizing an in vitro experiment model. Myometrial strips alongside the upper part of the low transverse uterine incisions were obtained at the time of the cesarean birth from 22 healthy, non-laboring, pregnant women, scheduled for elective cesarean birth at term. Strips were transferred to the laboratory and underwent dissection into tissue samples, each approximately 5 mm long, 2 mm wide, and 1 mm thick. In isolated muscle tissue baths, each tissue was attached to a stationary hook and the other end was attached to a force transducer and mounted for isometric recording under 2 gm of tension. Tissues were prepared under isometric conditions and underwent both spontaneous and oxytocin-induced contractions. Control experiments were performed simultaneously. Total of 11 participants with obesity and 11 normal-weight participants were enrolled. In both spontaneous and oxytocin-induced contractions, there was a significant reduction in amplitude of contractions between normal-weight and participants with obesity (P= 0.04, and P=0.049 in spontaneous and oxytocin-induced contractions respectively) and a significant reduction in frequency of contractions between groups (P= 0.01, and P=0.02 in spontaneous and oxytocin-induced contractions respectively). Obesity may impair the ability of the uterus to contract in labor which might contribute to the increased cesarean birth rate in women with obesity. This study reiterates the importance of preconception counseling on optimizing weight prior to pregnancy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

668 Uterorelxant effect of adiponectin and omentin on In Vitro human myometrial contractility

The onset of parturition in pregnant women with obesity is frequently delayed. Without induction, these women are nearly twice as likely as normal-weight women to have prolonged pregnancies even after control for birth weight. Adipokines are cell signaling mediators secreted by the adipose tissue, many of which are now known to be closely linked to metabolic regulation including smooth muscle function. In this study, we aimed to investigate the role of adiponectin, and omentin on the in vitro functional contractility of isolated myometrial samples. Myometrial strips alongside the upper part of the low transverse uterine incisions were obtained at the time of the cesarean birth from 22 healthy, non-laboring, pregnant women, scheduled for elective cesarean birth at term. In isolated muscle tissue baths, myometrial strips were prepared under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative doses of adiponectin and omentin in the concentration range of 1 nmol/L to 10 umol/L. Control experiments were performed simultaneously. Both adiponectin and omentin exerted significant uterorelaxant effect ( reduction in amplitude and frequency of contractions) on the myometrial samples, in both spontaneous and oxytocin-induced contractions, in vitro. The inhibitory effect was in the region of 36 % for adiponectin, and 33 % for omentin in tissue baths with spontaneous contractions and in the region of 31% for adiponectin and 30% for omentin in tissue baths with oxytocin-induced contractions. In this study, we show the inhibitory role of adiponectin and omentin on human myometrial contractility, in vitro. These findings reiterate the physiological role of metabolic changes associated with maternal weight on myometrial contractility. The cellular mechanisms, and the potential clinical implications are not fully understood which could be addressed in future studies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Improving Neonatal and Maternal Outcome by Inducing Mild Labor before Elective Cesarean Section: The Lacarus Randomized Controlled Trial

Background: Newborns delivered by elective cesarean section (CS) are at higher respiratory risk than those delivered vaginally or by CS proceeded by labor (secondary CS). The oxytocin challenge test (OCT) induces uterine contractions that trigger the release of fetal hormones regulating lung fluid clearance during transition from the uterine to an air-breathing environment. Objectives: The aim is to summarize current evidence and outline the Lacarus trial protocol. Methods: Literature review informed the design of a randomized placebo-controlled multicenter trial of OCT preceding elective CS in 1,450 women with a singleton pregnancy due for CS at >35 weeks gestation, without preceding contractions, rupture of the membranes, or antenatal steroids. OCT comprises the infusion of oxytocin 5 IU/500 mL Ringer lactate at a rate of 12 mL/h, doubling every 10 min until inducing 5 uterine contractions per 15-min interval. The primary endpoint is the occurrence of neonatal respiratory morbidity within 24 h after birth. Secondary endpoints include biochemical and physiological parameters of fetal and maternal well-being, such as breastfeeding rate and fetal plasma copeptin concentrations. Conclusion: This is the first trial to test the hypothesis that oxytocin-induced contractions before elective CS is a promising application of physiologic principles gleaned from natural birth to improve neonatal and maternal outcomes.

Clinically relevant concentrations of dexmedetomidine may reduce oxytocin-induced myometrium contractions in pregnant rats.

BackgroundRecently, there have been some trials to use dexmedetomidine in the obstetric field but concerns regarding the drug include changes in uterine contractions after labor. We aimed to evaluate the effects of dexmedetomidine on the myometrial contractions of pregnant rats.MethodsIn a pilot study, the contraction of the myometrial strips of pregnant Sprague-Dawley rats in an organ bath with oxytocin at 1 mU/ml was assessed by adding dexmedetomidine from 10-6 to 10-2 M accumulatively every 20 min, and active tension and the number of contractions were evaluated. Then, changes in myometrial contractions were evaluated from high doses of dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M). The effective concentrations (EC) for changes in uterine contractions were calculated using a probit model.ResultsActive tension and the number of contractions were significantly decreased at 10-3 M and 10-4 M dexmedetomidine, respectively (P < 0.05). A complete loss of contractions was seen at 10-2 M. Dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M) decreased active tension and the number of contractions in a concentration-dependent manner. The EC95 of dexmedetomidine for inhibiting active tension and the number of contractions was 5.16 × 10-2 M and 2.55 × 10-5 M, respectively.ConclusionsActive tension of the myometrium showed a significant decrease at concentrations of dexmedetomidine higher than 10-3 M. Thus, clinical concentrations of dexmedetomidine may inhibit uterine contractions. Further research is needed for the safe use of dexmedetomidine in the obstetrics field.

Leptin receptor stimulation in late pregnant mouse uterine tissue inhibits spontaneous contractions by increasing NO and cGMP

The adipokine, leptin exerts inhibitory effect on both spontaneous and oxytocin-induced contractions in myometrium. However, the mechanisms involved in leptin-induced effect are not clear. In the present study, we studied the altered characteristics of uterine contractions in the presence of leptin and the possible mechanisms of its effect in late pregnant (18.5 day) mouse uterus. We conducted functional, biochemical and molecular biology studies to demonstrate the mechanism of leptin-induced response. Leptin exerted an inhibitory response (Emax 40.5 ± 3.99%) on basal uterine contractions. The extent of inhibition was less than that obtained with known uterine relaxants, salbutamol (Emax103 ± 8.66%) and BRL-37344 (Emax 84.79 ± 8.12%). Leptin-induced uterine response was inhibited by leptin receptor antagonist SHLA and JAK-STAT pathway inhibitor, AG-490. The relaxant response was also subdued by NO-cGMP-PK-G pathway blockers L-NAME, 1400W, ODQ and KT-5823. Further, leptin enhanced the levels of NO and cGMP in uterine tissues. Also, SHLA, AG-490 and a combination of 1400 W and L-NAME prevented leptin-induced increase in NO. Similar effect was observed on cGMP levels in presence of leptin and SHLA. However, leptin did not influence CaCl2-induced response in potassium-depolarized tissues. We also detected leptin receptor protein in late pregnant mouse uterus located in endometrial luminal epithelium and myometrial layers. Real-time PCR studies revealed significantly higher expression of short forms of the receptor (ObRa and ObRc) in comparison to the long form (ObRb). In conclusion, the results of the present study suggest that leptin inhibits mouse uterine contraction by stimulating short forms of the leptin receptors and activating NO pathway in a JAK-STAT-dependent manner.

Effects of anesthetic agents on contractions of the pregnant rat myometrium in vivo and in vitro

BackgroundSeveral anesthetic agents are used in cesarean sections for both regional and general anesthesia purposes. However, there are no data comparing the in vivo effects of propofol, sevoflurane, and dexmedetomidine on the contraction of the myometrium in pregnant rats. The aim of this study was to investigate the effect of these anesthetic agents on myometrial contraction and elucidate the underlying mechanisms.MethodsContraction force and frequency changes in response to propofol, dexmedetomidine, or sevoflurane were evaluated in vivo and in vitro. To test the effect of arachidonic acid on myometrial contraction enhanced by dexmedetomidine, changes in myometrial contraction with dexmedetomidine after administration of indomethacin were evaluated. The amount of phosphorylated myosin phosphatase target subunit 1 (MYPT1) in the membrane fraction was expressed as a percentage of the total fraction by Western blot analysis.ResultsThis study demonstrated that dexmedetomidine enhances oxytocin-induced contraction in the myometrium of pregnant rats, whereas propofol and sevoflurane attenuate these contractions. The dexmedetomidine-induced enhancement of myometrial contraction force was abolished by the administration of indomethacin. Propofol did not affect oxytocin-induced MYPT1 phosphorylation, whereas sevoflurane attenuated oxytocin-induced MYPT1 phosphorylation.ConclusionsInhibition of myofilament calcium sensitivity may underlie the inhibition of myometrial contraction induced by sevoflurane. Arachidonic acid may play an important role in the enhancement of myometrial contraction induced by dexmedetomidine by increasing myofilament calcium sensitivity. Dexmedetomidine may be used as a sedative agent to promote uterine muscle contraction and suppress bleeding after fetal delivery.

Gestational and Hormonal Effects on Magnesium Sulfate\u2019s Ability to Inhibit Mouse Uterine Contractility

Magnesium sulfate is used as a tocolytic, but clinical efficacy has been seriously questioned. Our objective was to use controlled ex vivo conditions and known pregnancy stages, to investigate how 2 key factors, hormones and gestation, affect magnesium’s tocolytic ability. We hypothesized that these factors could underlie the varying clinical findings around magnesium’s efficacy. Myometrial strips were obtained from nonpregnant (n = 10), mid-pregnant (n = 12), and term-pregnant (n = 11) mouse uterus. The strips were mounted in organ baths superfused with oxygenated physiological saline at pH 7.4 and 37 °C. The effect of different concentrations of MgSO4 (2-20 mM) was examined on spontaneous and oxytocin-induced (0.5-1 nM) contractions. Contractile properties (amplitude, frequency, and area under the curve) were measured before and after application of magnesium. Magnesium sulfate had a dose-dependent inhibitory effect on both spontaneous and oxytocin-induced contractions but was less effective in the presence of oxytocin. In spontaneous contractions, magnesium was more potent as gestation progressed (P < .0001). In the presence of oxytocin, however, there were no significant gestational differences in its effects on contraction. The rapid onset and reversal of magnesium’s effects suggest an extracellular action on calcium entry. Taken together, we conclude that magnesium’s actions are influenced by both gestational state and hormones, such that, at least in mice, it is least effective in early gestation with oxytocin present and most effective at term in the absence of oxytocin. That magnesium is least effective preterm and oxytocin decreases its effectiveness throughout gestation, may explain its disappointing clinical effects as a tocolytic.

The effect of morbid obesity or advanced maternal age on oxytocin-induced myometrial contractions: an in vitro study.

The purpose of this study was to investigate myometrial contractility induced by oxytocin in women withadvanced maternal age (AMA) and morbid obesity(MO). We hypothesized that both oxytocin-pretreated and oxytocin-naïve myometrial tissues from women of AMA and women who are MO would exhibit poor myometrial contractility compared with women that are younger and of normal body mass index (BMI). This prospective in vitro study was conducted using myometrial samples obtained from women undergoing elective Cesarean deliveries. Three groups of patient were studied: control (≤ 35 yr; BMI, 20-24.9 kg·m-2), AMA (≥ 40 yr; BMI, 20-24.9 kg·m-2), and MO (≤ 35 yr BMI, ≥ 40 kg·m-2). Each myometrial strip was either pretreated with oxytocin 10-5 M or left in physiologic salt solution for two hours. This was followed by a dose-response testing to oxytocin (10-10 M to 10-5 M), during which contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. The MI of contractions was reduced in oxytocin-pretreated samples when compared with their oxytocin naïve counterparts in control (estimated difference -69%; 95% confidence interval [CI], -82 to -48; P < 0.001) and AMA groups (estimated difference, -44%; 95% CI, -68 to -2; P = 0.07). The MI of contractions was not different between oxytocin naïve and oxytocin-pretreated samples from MO women (estimated difference, -26%; 95% CI, -63 to 49; P = 0.46); however, it was significantly lower in these groups compared with oxytocin-naïve samples from the control group. Oxytocin pre-treatment reduced myometrial contractility in AMA and control group women compared with their oxytocin-naïve counterparts, as a function of the desensitization phenomenon. Attenuated oxytocin-induced myometrial contractility in MO women in both oxytocin-pretreated and oxytocin-naïve samples suggests that these women have intrinsically reduced uterine contractile ability. www.clinicaltrials.gov (NCT01865669; registered 28 May, 2013).

Pimpinella anisum extract attenuates spontaneous and agonist-induced uterine contraction in term-pregnant rats

Ethnopharmacology relevancePimpinella anisum is a well-known traditional medicinal herb which has been used in folk medicine as an antiulcer, anticancer, antibacterial and as a muscle relaxant. Aim of the studyThis study was performed to explore the modulatory effects of Pimpinella anisum on term-pregnant rat uterine contractility and to investigate its possible underlying mechanisms. Material and methodsIntact uterine strips without endometrial layer were isolated from female term-pregnant Wistar rats (22 days of gestation) and mounted in a tissue bath apparatus for in vitro isometric force recording. The effects of different concentrations of Pimpinella anisum extract (PAE) (1, 3, 5, and 7 mg/mL) were examined on uterine contractions generated spontaneously or induced with oxytocin (5 nmol/L), Bay K8644 (1 μmol/L), and carbachol (10 μmol/L). In some experiments, PAE was applied on depolarized myometrium in the presence of high-KCl solution (60 mmol/L). The effect on Ca2+ release was also examined. ResultsApplication of PAE significantly reduced uterine contractions generated spontaneously or induced with oxytocin, Bay K8644, and carbachol in a concentration-dependent manner (n = 7; P < 0.01). In depolarized myometrium, PAE significantly reduced the tonic force induced by high-KCl solution (n = 7; P < 0.01). PAE prevented oxytocin-induced transient contraction in the entire absence of external calcium (n = 7; P < 0.01). ConclusionThe present findings demonstrate the potentials of PAE to relax pregnant uterine contractions possibly by blocking Ca2+ entry via L-type calcium channels and inhibiting Ca2+ release from the internal store. The tocolytic effects of PAE may be a potential adjuvant against strong premature uterine contractions which threaten early pregnancy although clinical studies are required.

Ex-vivo inhibition of uterine contractility by the stem bark extracts of Omphalocarpum procerum P.Beauv. (Sapotaceae) in mouse models

Context: The plant Omphalocarpum procerum is used traditionally in Africa to manage female reproductive health issues such as infertility and menstrual cycle regulation. In the search for new therapies for the management of female reproductive issues, the plant O. procerum was investigated in this study. Aims: To determine the activity of the methanol extract of O. procerum stem bark (MOPS) on uterine contractility, as a measure to determine its usefulness in uterine contractility associated disorders. Methods: MOPS’ activity on spontaneous, oxytocin, KCl-induced contractions and in calcium-free solution was determined on the isolated uterus. Possible mechanisms of activity were determined using receptor and channel blockers. Results: MOPS inhibited spontaneous and oxytocin-induced contractions. MOPS also inhibited oxytocin-induced contractions in calcium-free solution. MOPS was also found to exert its inhibitory effect through interaction with β-adrenoceptors in the uterus. Conclusions: MOPS has been shown to inhibit uterine contractility in the non-pregnant and pregnant uterus primarily through the activation of β-adrenoceptors in the uterus.

Hyperlipidemia impairs uterine β-adrenergic signaling by reducing cAMP in late pregnant rats.

The aim of the present study was to reveal the effect of hyperlipidemia on β2- and β3-adrenergic signaling in late pregnant rat uterus. Hyperlipidemia was induced in female Wistar rats by feeding a high-fat high-cholesterol diet for 8 weeks before and after mating upto the 21st day of gestation. The effect of hyperlipidemia on β-adrenergic signaling was studied with the help of tension experiments, real-time PCR and cAMP ELISA in 21-day pregnant rat uterus. In tension experiments, hyperlipidemia neither altered the spontaneous contractility nor the oxytocin-induced contractions. However, it decreased the -logEC50 values of β2-adrenoceptor agonist, salbutamol and β3-adrenoceptor agonist, BRL37344. It also decreased the efficacy of adenylyl cyclase activator, forskolin. Further, there was a significant decrease in salbutamol and BRL37344-stimulated cAMP content in uterine tissues. However, there was no alteration in mRNA expressions of β2-adrenoceptor (Adrb2), β3-adrenoceptor (Adrb3) and Gs protein (Gnas) though there was a significant increase in the mRNA expression of Gi protein (Gnai). In conclusion, reduced cAMP content after beta-adrenergic receptor stimulation, which correlates with an increase in Gnai mRNA, may explain the mechanism of the impairment of uterine β-adrenergic signaling in hyperlipidemic pregnant rats. The clinical implication of the present study may relate to reduced myometrial relaxant response to β-adrenergic agonists in high fat-induced uterine dysfunction.

The Effect of Vitamin D3 on the Contractile Response of Isolated Rat Uterus

AbstractBackground: Vitamin D receptors (VDR) are expressed in many reproductive tissues indicating a potential role of vitamin D3-VDR in the regulation of reproductive functions. Nevertheless, the data about the effect of vitamin D3 in the uterus are scarce.Aim of Study: This study was designed to evaluate the potential effects of vitamin D3 on spontaneous, KCl-induced and oxytocin-induced contractions in the rat uterus in vitro.Material and Methods: The study was conducted on 10 healthy adult female albino non-pregnant rats. Full-thickness longitudinal muscle strips were dissected from each non-pregnant rat and then myometrial tension was recorded. The strips were mounted vertically in organ baths and exposed to vitamin D3 and different uterotonic agents to delineate the potential action of vitamin D3 on the rat myometrial contrac-tility. Spontaneous contractions were recorded using mechan-ical activity recording system. We evaluated the effects of 3 different dosed of vitamin D3 on spontaneous uterine contrac-tions; then on concentrated KCl-induced uterine contractions and oxytocin (OT)-induced uterine contractions. Furthermore, the effects of vitamin D3 on spontaneous uterine contractions pretreated with nifedipine; a voltage-gated L-type Ca2+ channel antagonist were investigated.Results: Vitamin D3 significantly inhibited the spontaneous uterine contractions in a dose dependent manner. Moreover, vitamin D3 inhibited the uterine contractions whether induced by oxytocin or concentrated KCl. Administration of nifedipine resulted in a significant decline in the force amplitude of spontaneous uterine contractions. In the presence of vitamin D3, the uterine relaxant effect of nifedipine was significantly augmented.Conclusions: The inhibitory effects of the in vitro admin-istration of vitamin D3 on rat uterus may yield novel insights into its therapeutic use. Further, it may be recommended to be used as a novel tocolytic agent for preventing unwanted uterine contractions in early pregnancy and relieving pain related to dysmenorrhea.

Curcuma longa aqueous extract possesses tocolytic potentials

Introduction: Contraction of the uterus is an important physiological phenomenon that determines the functionality of the uterus for pregnancy and abortion. Curcuma longa, a member of the ginger family (Zingiberracaeae) has been used in traditional medicine because of its various therapeutic properties. Curcuma longa is believed to be beneficial to the female reproductive system by preventing unwanted uterine activity in early pregnancy or treat preterm labour. There are however, no scientific facts verifying the effects on the uterus to support its folklore use as tocolytic agent. The aim of this study was to determine the effects of aqueous extract of Curcuma longa rhizome and its possible mechanism of action on uterine contraction. Methods: The Isolated longitudinal uterine strips were dissected from non-pregnant rats, mounted vertically in an organ bath chamber, and exposed to the aqueous extract of Curcuma longa rhizome at a concentration of 25 - 200 mg/ml. The effects of the extract at a concentration of 50 mg/ml on spontaneous and oxytocin-induced (10 nmol/L) contractions were investigated. Results: The results of the study revealed that the extract significantly (p &lt; 0.05) inhibited both spontaneous and oxytocin-induced uterine contractions (n = 10). The extract also inhibited oxytocin-induced contraction in the absence of exogenous calcium (n = 10). Significance: The result of this research has shown that Curcurma longa extract possesses or exerts tocolytic effect that delays uterine contraction in rats and this finding justify its folklore uses in traditional medicine to prevent unwanted uterine activity in early pregnancy or treat preterm labour.