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Dysfunctional labour (DL) is a major cause of maternal and neonatal deaths worldwide. The only clinically available drug is oxytocin which is about 50% effective. Therefore, the development of new effective drugs for DL is a necessity. The medicinal plant Brachystegia eurycoma Harms (synonym B. spiceaformis) is used for labour management in ethnomedicine. In the search for new lead compounds for DL therapy, the stem bark of B. eurycoma was subjected to bioactivity-guided fractionation procedures to elucidate its uterine-modulating activities and active compounds. B. eurycoma stem bark extract (BE) was fractionated via vacuum liquid chromatographic techniques. The fractionation process was guided by ex vivo uterine contractility assays on the mouse uterus, performed using spontaneous, oxytocin, and high KCl-induced contractility assays. Furthermore, the characterization of the chemical constituents was performed using nuclear magnetic resonance (NMR) and mass spectrometry (MS). BE produced dual effects on uterine contractility which was dependent on the reconstitution period. The freshly prepared crude extract (BEF) inhibited uterine contractility (IC50 amplitude = 0.8 ± 0.1 mg/ml; IC50 frequency = 1.4 ± 0.2 mg/ml). However, contractility was augmented when the reconstituted extract was stored for 24 h and beyond (BES) (EC50 amplitude = 0.2 ± 1.2 mg/ml; EC50 frequency = 0.91 ± 1.2 mg/ml). In addition, the compounds caffeine, genistein, and prunetin were identified from the potent BE fractions via the different spectroscopic and spectrometric tools. This study demonstrated a storage-dependent dual effect of BE where BEF induced inhibition and BES augmented uterine contractility. Findings from this study also suggest that caffeine and phytoestrogens contributed to the uterine-modulating activities of BE. Thus, further investigation of these compounds in combination and as separate lead compounds is required for DL therapeutic management.

Objective: The non‐pregnant uterus shows an intrinsic contractility pattern, actively involved in early reproductive processes. Uterine contractility is characterized by endometrial waves that originate from the junctional zone and varies throughout the menstrual cycle due to fluctuations in the concentrations of hormones. The aim of this study was to compare the uterine contractility patterns in the periovulatory phase in a group of patients with isolated adenomyosis and a group of healthy women using transvaginal ultrasound (TVUS). Methods: From March 2019 to March 2021, we enrolled consecutive nulliparous patients in the periovulatory phase of the menstrual cycle, divided in patients with isolated adenomyosis (group A, n = 18) and healthy patients in the control group (group B, n = 18). Patients who met the inclusion criteria underwent TVUS for the study of uterine contractility: the uterus was scanned on sagittal plane for 3 min and all the movies were recorded. Then, static images and video were evaluated offline and the uterine contractility patterns were defined. Results: The patients belonging to the study group had a higher incidence of painful symptoms (dysmenorrhea, 6.11 ± 2.81 vs 1.39 ± 2.17; chronic pelvic pain, 2.56 ± 3.01 vs 0.39 ± 1.04) and a larger uterine volume (137.48 ± 117.69 vs 74.50 ± 27.58 cm3; P = 0.04). Regarding the uterine contractility, a statistically significant difference was observed about the retrograde patterns (group A, 27.8% vs group B, 72.2%, P < 0.01) and opposing (group A, 38.9% vs, group B, 5.6%, P = 0.02). Conclusion: The study confirms the presence of altered uterine peristalsis in the periovulatory phase in patients with adenomyosis. The abnormal uterine peristalsis could lead to both structural and functional changes, which are the basis of the clinical manifestations of adenomyosis and the perpetuation of the anatomical damage. Synopsis: The abnormal uterine peristalsis could lead to both structural and functional changes, which are the basis of the clinical manifestations of adenomyosis and the perpetuation of the anatomical alteration. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to compare performance of a maternal surface electrode patch with ultrasound- and tocodynamometer-based monitoring to detect fetal heart rate and uterine contractility in late preterm labors. Study Design Thirty women between 34 0/7 and 36 6/7 weeks' gestation were monitored simultaneously with a Doppler/tocodynamometer system and a wireless fetal–maternal abdominal surface electrode system. Fetal and maternal heart rate and uterine contraction data from both systems were compared. Reliability was measured by the success rate and percent agreement. Deming regression and Bland–Altman analysis estimated the concordance between the systems. Uterine contractions were assessed by visual interpretation of monitor tracings. Results The success rate for the surface electrode system was 89.5% (95% confidence interval [CI], 85.7–93.3), and for ultrasound it was 88.4% (95% CI, 84.9–91.9; p = 0.73), with a percent agreement of 88.1% (95% CI, 84.2–92.8). Results were uninfluenced by the patients' body mass. The mean Deming slope was 1 and the y-intercept was −3.0 beats per minute (bpm). Bland–Altman plots also showed a close relationship between the methods, with limits of agreement less than 10 bpm. The percent agreement for maternal heart rate was 98.2% (95% CI, 97.4–98.8), and for uterine contraction detection it was 89.5% (95% CI, 85.5–93.4). Conclusion Fetal heart rate and uterine contraction monitoring at 34 0/7 to 36 6/7 weeks using abdominal surface electrodes was not inferior to Doppler ultrasound/tocodynamometry for fetal–maternal assessment. Registration clinicaltrials.gov/February 20, 2017/identifier NCT03057275. Key Points Monitoring the preterm fetal heart rate with surface electrodes is feasible. Preterm contractions can be monitored with surface electrodes. The technique was noninferior to standard external monitors. [ABSTRACT FROM AUTHOR]

Aims: Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with β2-mimetic terbutaline in an isolated organ bath and to perform in vivo smooth muscle electromyographic studies in pregnant rats. The modifications in uterine cAMP/cGMP levels were also detected. Main methods: Contractions of non-pregnant and 5/15/18/20/22-day pregnant uterine rings were measured in an isolated organ bath system in the presence of sildenafil alone or with terbutaline. The uterine levels of cAMP and cGMP were determined by commercial ELISA assays. The in vivo efficacy of the combination was measured by smooth muscle electromyography. Key findings: Sildenafil reduced uterine contractions in vitro and in vivo; additionally, terbutaline significantly increased the uterorelaxant effect of sildenafil in the lower concentration or dose ranges. Terbutaline enhanced the cGMP level increasing effect of sildenafil. Significance: The co-administration of sildenafil and terbutaline could be a promising tocolytic combination to reduce maternal and foetal adverse events and increase efficacy.

Introduction: Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2‐mimetic terbutaline and magnesium sulfate (MgSO4) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia‐inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. Material and methods: In the isolated organ bath studies, rhythmic contractions of 22‐day‐ pregnant Sprague–Dawley rats were stimulated with KCl, and cumulative dose–response curves were constructed in the presence of MgSO4 or terbutaline. The uterus‐relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+‐poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Results: Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+‐poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia‐inducing effect of terbutaline in late pregnant rats. Conclusions: The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia‐inducing side effect of terbutaline. [ABSTRACT FROM AUTHOR]

Scopolamine is a parasympatholytic drug that can modulate uterine contractile activity. Based on the hypothesis that deficiency in uterine contractility is a cause of Repeat Breeder (RB) syndrome in cows, this study aimed to evaluate the efficacy of scopolamine administration in RB cows, on the day of heat, in increasing conception rates. Forty RB cows were randomly divided into treated group [T; 20 cows treated with scopolamine butylbromide 40 mg/100 kg of body weight (BW) by the intramuscular (IM) route after clinical confirmation of heat (T0)] and the control group [C; 20 cows treated with 2 mL/100 kg of BW of saline solution, IM, at T0]. Twelve hours later (T1), all of the cows were artificially inseminated (AI). Blood plasma-progesterone (P4), hydroxyproline, and prostaglandin F2α metabolite (PGFM), concentrations were assessed at T0 and T1. Additionally, the uterine tone was evaluated by transrectal palpation. Conception rates were recorded. Drug administration increased the conception rates in group T to 80% unlike group C (25%) (P < 0.0001). Higher PGFM concentration levels were registered in the treated group than in the control group. The higher PGF2α secretion in pregnant cows of the T group may have reduced the P4 levels, making conception possible. Scopolamine administration at the time of heat can improve uterine contractility. This makes it more suitable for promoting conception in RB cows, where hormonal alterations and contractile and biochemical deficits are responsible for the syndrome. • This study evaluated scopolamine use in repeat breeder cows to improve conception rates. • Scopolamine was administered at oestrus manifestation. • Scopolamine improved uterine tone. • Blood PGFM and P4 were higher and lower, respectively in the treated versus control groups. • Scopolamine can improve uterine environmental conditions promoting conception. [ABSTRACT FROM AUTHOR]

Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of Escherichia coli (E. coli)-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the E. coli group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10−6 M) reduced the amplitude and frequency in the myometrium of the E. coli group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the E. coli group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10−6 M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10−5 M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation. [ABSTRACT FROM AUTHOR]

Statins are 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor drugs that lead to serum-cholesterol-lowering effects. Rosuvastatin, a third-generation statin, has shown better results in reducing cholesterol concentrations when compared to other widely prescribed statins. Recent studies by our group reported that rosuvastatin impairs reproductive function in rats possibly by disrupting the reproductive-endocrine axis. In this study, we evaluated whether rosuvastatin presents estrogenic or antiestrogenic effects, by an in vivo uterotrophic assay in rats, and investigated the direct effect of this drug upon rat uterine tissue contractility both in non-gravid and gravid periods. Rosuvastatin exposure in vivo at doses of 0 (control), 3, and 10 mg/kg/d was not associated with estrogenic or antiestrogenic effects on uterine tissue. However, in vivo (doses of 0, 3, and 10 mg/kg/d) and ex vivo (concentrations of 0, 1, 10, and 100 µg/mL) exposures to this drug were related to alterations in uterine basal contraction pattern. Furthermore, in vivo and ex vivo rosuvastatin exposures potentially modulate the action of uterine contraction inducers carbachol, norepinephrine, and prostaglandin E2. Thus, rosuvastatin can affect uterine physiology not necessarily by an endocrine mechanism related to the estrogen signaling, but possibly by its pleiotropic effects, with indirect tissue and cellular interactions, since in vivo and ex vivo exposures of uterine fragments to rosuvastatin presented different responses in uterine contractile parameters, which require further studies upon the precise mechanism of action of this drug in female reproductive function. [ABSTRACT FROM AUTHOR]

Objective. This study aims to use recurrence quantification analysis (RQA) of uterine vectormyometriogram (VMG) created from the slow wave (SW) and high wave (HW) bands of electrohysterogram (EHG) signals and assess the directionality of the EHG activity (horizontal or X , vertical or Y ) in normal-weight (NW) and overweight (OW) women during the first stage of labor. Approach . The study involved 41 parturient women (NW = 21 and OW = 20) during the first stage of labor, all of whom were attended at the Gynecology and Obstetrics Hospital of the Maternal and Child Institute of the State of Mexico in Toluca, Mexico. Twenty-minute EHG signals were analyzed in horizontal and vertical directions. Linear and nonlinear indices such as dominant frequency (Dom), Sample Entropy (SampEn), and RQA measures of VMG were computed for SW and HW bands. Main results . Significant differences in SampEn and Dom were observed in the SW band between NW and OW in both X and Y directions, indicating more regular dynamics of electrical uterine activity and a higher Dom in NW parturient women compared to OW women. Additionally, the RQA indices calculated from the VMG of SW were consistent and revealed that NW women exhibit more regular dynamics compared to OW women. Significance . The study demonstrates that RQA of VMG signals and EHG directionality differentiate uterine activity between NW and OW women during the first stage of labor. These findings suggest that the uterine vector may become more periodic, predictable, and stable in NW women compared to OW women. This highlights the importance of tailored clinical strategies for managing labor in OW women to improve maternal and infant outcomes., (Creative Commons Attribution license.)

Background: In obesity, the adipose tissue becomes a very significant endocrine organ producing different factors called adipokines, such as leptin, adiponectin and kisspeptin; however, no data are available about their actions on uterine contraction in obese pregnant rats. Our aim was to study the impact of obesity on pregnant uterine contraction in a rat model. Methods: Obesity was induced by the consumption of a high fat high sucrose diet (HFHSD) for 9 weeks, including pregnancy. Glucose tolerance, sex hormone, cytokine and adipokine levels were measured. Uterine contractions and cervical resistance, as well as their responses to adipokines, were tested along with the expressions of their uterine receptors. Results: HFHSD increased body weight, and altered glucose tolerance and fat composition. The uterine leptin and kisspeptin pathway affect increased. The levels of proinflammatory cytokines were reduced, while the plasma level of progesterone was increased, resulting in weaker uterine contractions, and improving the uterine relaxing effects of adipokines. HFHSD reduced cervical resistance, but the core effect of adipokines is difficult to determine. Conclusions: Obesity in pregnant rats reduces uterine contractility and cytokine-induced inflammatory processes, and therefore obese pregnant rat methods are partially applicable for modelling human processes. [ABSTRACT FROM AUTHOR]

Uterine inflammation is a common pathology in animals, leading to disturbances in reproductive processes and reduced production profitability. Pituitary adenylate cyclase-activating peptide (PACAP) effects at the uterine level during inflammation are not known. In the current study, we analyzed the relative PACAP type 1 receptor (PAC1R) mRNA transcript and protein abundances in the myometrium (MYO), as well s PACAP and PAC1R involvement in the contractile function of inflamed pig uterus. To that end, E. coli suspension (E. coli group) or saline (SAL group) was injected into the uterine horns or laparotomy was performed (CON group). Eight days after the bacteria injections, severe acute endometritis and a reduced relative abundance of PAC1R protein in the MYO were observed. Compared to the period before PACAP in vitro administration, PACAP (10−7 M) in the CON and SAL groups decreased in amplitude in the MYO and endometrium (ENDO)/MYO, whereas in the E. coli group, increased amplitude in the MYO and reduced amplitude in the ENDO/MYO were observed. In the E. coli group, PACAP enhanced the amplitude in the MYO (10−7 M) and decreased the amplitude in the ENDO/MYO (10−8 M) compared with other groups. PACAP (10−7 M) increased the frequency of both kinds of strips in the CON and SAL groups compared with the pretreatment period. PACAP (both doses) did not significantly change the frequency in the E. coli group, whereas in response to PACAP (10−7 M), the frequency was reduced compared to other groups. In the MYO, PAC1R antagonist decreased the amplitude reduction (CON and SAL groups) and reversed a rise in PACAP (10−7 M)-evoked amplitude (E. coli group). PAC1R blocking reversed (MYO) and abolished (ENDO/MYO) the stimulatory effect of PACAP (10−7 M) on the frequency (CON and SAL groups). PAC1R antagonist and PACAP (10−7 M) evoked the appearance of frequency depression in both kinds of strips (E. coli group). In summary, in pigs, severe acute endometritis reduces the relative abundance of PAC1R protein in the MYO, and PAC1R mediates the influence of PACAP on inflamed uterus contractility. [ABSTRACT FROM AUTHOR]

Stress responses vary throughout pregnancy and impact of late gestational variable stress (LGVS) with vitamin C supplementation on uterine contractility is barely explored. This study investigates fetal weight outcome and in-vitro uterine contractile responses to pharmacological agents during LGVS exposure. Twenty four nulliparous pregnant rats were divided into four groups of six. During gestation days 10–19, groups 1 & 2 received normal saline and vitamin C (10 mg/kg) respectively. Groups 3 and 4 were exposed to stress (sleep deprivation, predator exposure, immobility, rapid cage changes, noise, and foreign object) with group 4 concurrently supplemented with vitamin C (10 mg/kg). Serum cortisol, oxidative bio-markers, fetal weights and in-vitro contractile responses of excised uterine tissue to acetylcholine (Ach), oxytocin, calcium chloride (CaCl2), potassium chloride (KCl), diclofenac, and magnesium ions were determined. Malondialdehyde activity and cortisol were significantly increased in variable stress only exposed group when compared with control and vitamin C supplemented groups. Fetal body weights, superoxide dismutase and catalase activity were significantly reduced in variable stress only exposed group. Significantly impaired contractile responses to Ach, CaCl2 & KCl in variable stress only exposed group were modulated in vitamin C supplemented groups. Impaired contractile response to oxytocin was however not reversed. Relaxation responses to diclofenac and magnesium ions were statistically unaltered across groups. Impaired fetal weights and uterine contractile activity to Ach, CaCl2 and KCl during LGVS was modulated by vitamin C supplementation. Impaired oxytocin contractile activity was however unreversed. [ABSTRACT FROM AUTHOR]

Objective: Women undergoing IVF who have had a previous c-section (CS) have a lower live birth rate than those with a previous vaginal delivery. However, the precise underlying mechanisms need clarification. Does a previous CS affect the pattern of uterine contractility?., Methods: Prospective evaluation in patients undergoing frozen blastocyst embryo transfer in medicated endometrial preparation cycles. Twenty patients were included in groups: A/nulliparous. B/previous vaginal delivery. C/ previous CS without a niche, whereas fifteen patients were recruited in group D (CS and a niche). Patients employed estradiol compounds and 800 mg vaginal progesterone. A 3D-scan was performed the transfer-day where uterine contractility/minute was recorded., Results: Baseline characteristics (age, BMI, smoking, endometrial thickness) were similar. Mean frequency of uterine contractions/minute was similar between groups (1.15, 1.01, 0.92, and 1.21 for groups A, B, C, and D, respectively). There was a slight increase in the number of contractions in patients with a sonographic niche versus controls, not reaching statistical significance (p=0.48). No differences were observed when comparing patients with a previous C-section (regardless of the presence of a niche) to those without a C-section, either nulliparous (p=0.78) or with a previous vaginal delivery (p=0.80). The frequency of uterine contractions was similar between patients who achieved a clinical pregnancy and those who did not (1.19 vs. 1.02 UC/min, p=0.219, respectively)., Conclusions: Our study found no significant difference in the frequency of uterine contractility between patients with or without a previous C-section or sonographic diagnosed niche. Further investigation is necessary to understand the physiological mechanisms affecting implantation in patients with isthmocele.

For successful fertilization, a transfer system named "rapid sperm transport" generated by uterine contractions plays a crucial role. The purpose of this in vivo study was to investigate the effect of buserelin, a GnRH agonist widely used for ovulation induction after mating or artificial insemination, on bovine uterine contractility which supports rapid sperm transport at estrus. In vivo uterine contractile activity was measured by intrauterine pressure recording technique. In the study, the spontaneous uterine contractile activities of 28 cows at estrus were observed for 30 min. The cows were randomly divided into 4 treatment groups which have 7 cows each of and were injected appropriate agents as follows; two different clinical doses of buserelin (10.5 µg, 21 µg), oxytocin (50 IU) and control (placebo). Following treatment, drug-induced uterine activity was measured for 60 min. There were no differences in terms of frequency in all groups observed. Oxytocin which is known as an effective uterotonic increased the amplitude and area under curve of contraction at estrus. Two different doses of buserelin were observed to have no effect on uterine contractile activity in cows throughout 60 min. It was concluded that GnRH has no function on bovine uterine contractility which plays a role in sperm transportation at estrus. [ABSTRACT FROM AUTHOR]

Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of Escherichia coli (E. coli)-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the E. coli group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10−6 M) reduced the amplitude and frequency in the myometrium of the E. coli group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the E. coli group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10−6 M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10−5 M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation.

Uterine inflammation is a common pathology in animals, leading to disturbances in reproductive processes and reduced production profitability. Pituitary adenylate cyclase-activating peptide (PACAP) effects at the uterine level during inflammation are not known. In the current study, we analyzed the relative PACAP type 1 receptor (PAC1R) mRNA transcript and protein abundances in the myometrium (MYO), as well s PACAP and PAC1R involvement in the contractile function of inflamed pig uterus. To that end, E. coli suspension (E. coli group) or saline (SAL group) was injected into the uterine horns or laparotomy was performed (CON group). Eight days after the bacteria injections, severe acute endometritis and a reduced relative abundance of PAC1R protein in the MYO were observed. Compared to the period before PACAP in vitro administration, PACAP (10−7 M) in the CON and SAL groups decreased in amplitude in the MYO and endometrium (ENDO)/MYO, whereas in the E. coli group, increased amplitude in the MYO and reduced amplitude in the ENDO/MYO were observed. In the E. coli group, PACAP enhanced the amplitude in the MYO (10−7 M) and decreased the amplitude in the ENDO/MYO (10−8 M) compared with other groups. PACAP (10−7 M) increased the frequency of both kinds of strips in the CON and SAL groups compared with the pretreatment period. PACAP (both doses) did not significantly change the frequency in the E. coli group, whereas in response to PACAP (10−7 M), the frequency was reduced compared to other groups. In the MYO, PAC1R antagonist decreased the amplitude reduction (CON and SAL groups) and reversed a rise in PACAP (10−7 M)-evoked amplitude (E. coli group). PAC1R blocking reversed (MYO) and abolished (ENDO/MYO) the stimulatory effect of PACAP (10−7 M) on the frequency (CON and SAL groups). PAC1R antagonist and PACAP (10−7 M) evoked the appearance of frequency depression in both kinds of strips (E. coli group). In summary, in pigs, severe acute endometritis reduces the relative abundance of PAC1R protein in the MYO, and PAC1R mediates the influence of PACAP on inflamed uterus contractility.

Does uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? Prospective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5–7 days after embryo transfer (ET5–7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. Uterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5–7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5–7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5–7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5–7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5–7 in women with ongoing pregnancies. This study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF. [ABSTRACT FROM AUTHOR]

Resveratrol (RSV), a plant-derived polyphenol, demonstrates broad-spectrum health benefits, including anti-proliferative, anti-inflammatory, antidiabetic, anti-ischemic and antioxidant effects. The aim of this review is to give an important heads-up regarding the influence of RSV as a phytoestrogen, RSV effects on most common pregnancy-related complications, as well as its impact on the embryogenesis, spermatogenesis, and women’s reproductive health. Considering the important implications of RSV on human reproductive health, this overview could provide a groundwork, encouraging more detailed research at the clinical level.

Contractions of the non-pregnant uterus play a key role in fertility. Yet, the electrophysiology underlying these contractions is poorly understood. In this paper, we investigate the presence of uterine electrical activity and characterize its propagation in unstimulated ex vivo human uteri. Multichannel electrohysterographic measurements were performed in five freshly resected human uteri starting immediately after hysterectomy. Using an electrode grid externally and an electrode array internally, measurements were performed up to 24 h after hysterectomy and compared with control. Up to 2 h after hysterectomy, we measured biopotentials in all included uteri. The median root mean squared (RMS) values of the external measurements ranged between 3.95 μV (interquartile range (IQR) 2.41–14.18 μV) and 39.4 μV (interquartile range (IQR) 10.84–105.64 μV) and were all significantly higher than control (median RMS of 1.69 μV, IQR 1.13–3.11 μV), consisting of chicken breast meat. The RMS values decreased significantly over time. After 24 h, the median RMS (1.27 μV, IQR 0.86–3.04 μV) was comparable with the control (1.69 μV, IQR 1.13–3.11 μV, p = 0.125). The internal measurements showed a comparable pattern over time, but overall lower amplitude. The measured biopotentials propagated over the uterine surface, following both a plane-wave as well as an erratic pattern. No clear pacemaker location nor a preferred propagation direction could be identified. These results show that ex vivo uteri can spontaneously generate propagating biopotentials and provide novel insight contributing to improving our understanding of the electrophysiology of the human non-pregnant uterus. [ABSTRACT FROM AUTHOR]

The leaf of Moringa oleifera (Lam) Moringaceae, is globally accepted in ethnomedicine and particularly used to tackle malnutrition and enhance breast milk production in resource-limited settings. It is reported to be laden with a wide array of interesting bioactive plant metabolites. However, its safety at conception and during pregnancy has not been well reported notably in Nigeria. This work investigated the in vitro and in vivo uteroactive and contraceptive potentials of cold and hot aqueous extracts of M. oleifera leaves (MOL) commonly used in Nigerian Traditional Medicine. In addition, we determined the physicochemical characteristics of the freeze-dried aqueous extracts and powder. Powdered MOL (100 g each, 1:10 w / v) was extracted in the cold (room temperature) and hot (boiling) distilled water. The in vitro protocol involved the dose-dependent effect of aqueous extracts of MOL on the tension produced by the isolated uteri of non-pregnant rats using organ bath. Uterine contractility and contraceptive properties of MOL were assessed in vivo using female Wistar rats (150–170 g). Particle morphology, size, polydispersity index and zeta potential of MOL were determined. The in vitro administration of cold and hot aqueous extracts of MOL significantly (p <.05) produced uterine contractility with varying intensities. Contractile effect of cold MOL aqueous extract (89.7%) was higher than that of hot MOL (50.6%). In vivo , MOL cold aqueous extracts administered before and after mating, respectively produced 100% and 80% inhibition of conception, while 96.6% and 58% effect was comparatively produced by hot aqueous extracts of MOL. This work has provided useful data on MOL, a commonly consumed medicinal preparation/food supplement and the possible implications of its intake before conception, at conception and during pregnancy. • M. oleifera leaves may not be safe at conception and during pregnancy. • M. oleifera leaves growing in Nigeria prevented conception in tested rodents. • Thesame leaves induced abortions and myometrial uterine contractions in Wistar rats. • Physico-chemical characters suggest the powdered leaves are more stable. • This may account for the preference for MOL products sold in powder. Edited by NE Madala [ABSTRACT FROM AUTHOR]

This study analyzed the effect of inflammation on acetylcholine (ACh)-induced muscarinic receptors (MR)2 and MR3 conducted contractility of the porcine uterus. On Day 3 of the estrous cycle, either E.coli suspension (E.coli group) or saline (SAL group) was injected into uterine horns or laparotomy was performed (CON group). Eight days later, infected gilts developed severe acute endometritis. Compared to the period before ACh treatment, ACh (10−5 M) increased the tension in myometrium (MYO) and endometrium/myometrium (ENDO/MYO) of the CON group (P < 0.01) and in ENDO/MYO of the SAL group (P < 0.01), the amplitude in strips of the CON (P < 0.05) and SAL (MYO: P < 0.05, ENDO/MYO: P < 0.001) groups and the frequency in strips of the CON (MYO: P < 0.01, ENDO/MYO: P < 0.001) and SAL (P < 0.01) groups. In the E.coli group, ACh (10−5 M) reduced the amplitude in MYO (P < 0.05) and ENDO/MYO (P < 0.001), increased the frequency in MYO (P < 0.01) and ENDO/MYO (P < 0.001) and did not change (P > 0.05) the tension. ACh (10−5 M) in ENDO/MYO of the E.coli group, reduced the tension compared to the CON group (P < 0.05) and the amplitude compared to other groups (P < 0.001), while increased the frequency in relation to the SAL group (P < 0.05). MR2 antagonist (AF-DX 44 116) and ACh (10−5 M) reduced (by 16.92%, P < 0.01) the tension in MYO of the CON group and increased (P < 0.01) it in the E.coli group compared to the period before antagonist and ACh addition. In MYO of the SAL group, the tension was increased (P < 0.01) in response to MR3 antagonist (4-DAMP) and ACh (10−7, 10−6 M). In the E.coli group, these substances did not change (P > 0.05) the tension, but it was lower (P < 0.001) in MYO (ACh: 10−7 M) and ENDO/MYO (ACh: 10−5 M) than in the SAL group. MR2 or MR3 antagonists and ACh (10−5 M) increased (P < 0.05-0.001) the amplitude in strips of the CON and SAL groups and reduced it in the E.coli group (P < 0.001) compared to the period before antagonists and ACh use. This parameter in the E.coli group was lower (P < 0.001) after using MR2 or MR3 antagonists and ACh (10−6, 10−5 M) than in other groups. Both antagonists and ACh (10−5 M) reduced the frequency in the CON, SAL (P < 0.05) and E.coli (MR2 antagonist: P < 0.01, MR3 antagonist: P < 0.05) groups compared to period before antagonists and ACh addition. Data show that ACh reduces the contractility of the inflamed porcine uterus by MR2 and MR3, which suggests that pharmacological modulation of these receptors can be used to raise the contractility of an inflamed uterus. • Acetylcholine increases contractility of healthy pig uterus. • Acetylcholine drops amplitude and raises contractile frequency of inflamed pig uterus. • In inflamed pig uterus acetylcholine did not significantly change the tension. • Acetylcholine affects inflamed uterus contractility by muscarinic receptors 2 and 3. [ABSTRACT FROM AUTHOR]

Background and aim: Alpha-tocopherol has been implicated in reproduction processes, and deficiency of phylloquinone has been associated with serious complications in pregnancy. This study was therefore aimed at investigating the effects of phylloquinone and alpha-tocopherol on uterine contractility and female reproductive function using mouse models. Materials and methods: Both in vivo and ex vivo animal models were employed and designed to assess changes on uterine contractility and reproductive functions in the non-pregnant uterus. The effect of alpha-tocopherol and phylloquinone on spontaneous uterine contractions, oxytocin-induced uterine contractions (11.82 nM) and high KCl-induced tonic uterine contractions (80 mM) were assessed. The effect of subcutaneous administration of alpha-tocopherol (10 mg/kg) on reproductive hormone levels and reproductive tissues were also determined. Results: Alpha-tocopherol increased the force of contractions while phylloquinone decreased the force of uterine contractions. Plasma levels of luteinizing hormone (P

Background: Preterm birth is the most common cause of neonatal morbidity and mortality and a common precedent to lifelong disability. Current treatment has minimal efficacy. Objective: We assessed the role of isozymes of the protein kinase C (PKC) family in regulating the phosphorylation of myosin regulatory light chains (RLCs), which regulate uterine contractility. We also explored the mechanisms through which these isozymes function. Study Design: We used a previously characterized and validated quantitative in-cell Western (ICW) assay to measure site-specific phosphorylations on myosin RLC and CPI-17. Cultures of human uterine myocytes (hUM) were treated with the potent contractile stimulant oxytocin to induce uterine contractility or a pharmacological mimic of diacyl-glycerol to stimulate the conventional and novel isozymes of the PKC family. Combinations of isozyme-selective inhibitors were used to determine the effects of the conventional and novel classes of isozymes. Results: Stimulation of PKC using phospho-dibutyrate caused immediate, concentration-dependent inhibition of uterine activity ex vivo. Using the ICW assay with hUM, the oxytocin-stimulated increase in the pro-contractile phosphorylations of myosin RLCs at serine19 and threonine18 was completely inhibited by prior treatment with phorbol-12-myristate-13-acetate, which stimulates both convention and novel classes of isozymes. Our results suggest that the conventional class of isozymes cause a reduction in phosphorylations at serine19 and threonine18 by reducing activity of myosin light chain kinase. The novel class of isozymes has 2 mechanisms of action: the first is activation of CPI-17 through phosphorylation at threonine38, which results in reduced activity of myosin light chain phosphatase and increased levels of activated myosin RLC; the second is increased phosphorylation of the N-terminal region of myosin RLC. Conclusions: Specific agonists for the conventional isozymes or inhibitors of the novel isozymes of the PKC family could be useful pharmacological agents for regulation of uterine activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Chorioamnionitis is associated with an increased risk of cesarean delivery and uterine atony. We hypothesized that the onset of maternal fever is temporally associated with decreased uterine contractility. Study Design: Retrospective cohort. Setting: Academic center. Patients: Term participants who developed a fever in the setting of an intrauterine pressure catheter. Main Outcome Measure: Montevideo units (MVUs) and oxytocin dose at time 0 (first oral temperature ƶ±C) and in the five 1-hour blocks preceding and following T0. Analysis: Montevideo units relative to the onset of fever. Results were adjusted for oxytocin dose and parity in a mixed-effects model. Results: One hundred participants were included. Uterine contractility was maintained for 2 hours after the onset of maternal fever but thereafter significantly and steadily declined by an average of 6.9 + 3.2 MVU/h (P = .03), despite the absence of a parallel decline in oxytocin exposure. Multiparas and nulliparas showed a similar pattern of waning uterine contractility. Patients who delivered vaginally maintained contractility, while those who delivered via cesarean had diminishing contractility (P = .01). The postpartum hemorrhage (PPH) rate (postpartum bleeding requiring treatment) was 32%. Conclusions: A decline in myometrial contractility occurs 2 hours following the onset of maternal fever. Increased risk of cesarean delivery appears to be directly associated with waning uterine contractility and decreased uterine responsiveness to oxytocin. Clinically, close attention should be given to maintaining adequate uterine contractions following a diagnosis of suspected chorioamnionitis. The likelihood of successful vaginal delivery may decrease over time, and the risk of PPH is clinically significant. [ABSTRACT FROM AUTHOR]

Objective: Abnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions. Study design: Female non-pregnant Sprague–Dawley rats (N = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect. Results: Screening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (−17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (−51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women. Conclusion: Our data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

Aims: Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with β 2 -mimetic terbutaline in an isolated organ bath and to perform in vivo smooth muscle electromyographic studies in pregnant rats. The modifications in uterine cAMP/cGMP levels were also detected., Main Methods: Contractions of non-pregnant and 5/15/18/20/22-day pregnant uterine rings were measured in an isolated organ bath system in the presence of sildenafil alone or with terbutaline. The uterine levels of cAMP and cGMP were determined by commercial ELISA assays. The in vivo efficacy of the combination was measured by smooth muscle electromyography., Key Findings: Sildenafil reduced uterine contractions in vitro and in vivo; additionally, terbutaline significantly increased the uterorelaxant effect of sildenafil in the lower concentration or dose ranges. Terbutaline enhanced the cGMP level increasing effect of sildenafil., Significance: The co-administration of sildenafil and terbutaline could be a promising tocolytic combination to reduce maternal and foetal adverse events and increase efficacy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Beta-sitosterol (β-sitosterol) is one of the several phytosterols widely studied for its potential to reduce benign prostatic hyperplasia and blood cholesterol levels. Objective: In the present study, the effects of β-sitosterol on spontaneous and agonist-induced contractions in in vitro nonpregnant human uterus with respect to prostaglandin E2 (PGE2) were investigated. Materials and Methods: Myometrial strips, measuring approximately 15 mm × 4 mm × 2 mm, were attained from hysterectomy samples of premenopausal women. Longitudinal muscle strips were mounted on tissue baths, under physiological conditions, to measure their isometric contraction. The effects of cumulative amounts of β-sitosterol on spontaneous motility in the absence and presence of prazosin, atropine, fulvestran, indomethacin, or ethylenediaminetetraacetic acid (EDTA), and on agonist-induced motor activity, were examined. Results: On strips in the follicular phase, both β-sitosterol (1-100 μg/ml) and PGE2 (0.1-10 μg/ml) increase, in a concentration-dependent manner, muscular basic tonus and amplitude and frequency of spontaneous uterine contractions; whereas on strips obtained during periovulatory phase, β-sitosterol and PGE2 cause inhibition of uterine motility. For contractile response, the effective concentrations (EC50) were 47.8 μg/ml and 5.19 μg/ml, respectively. Unlike indomethacin, the tissue pretreatment with prazosin, fulvestran, atropine, or ethylenediaminetetraacetic acid did not affect the contractile uterine responses to β-sitosterol. Furthermore, the β-sitosterol was able to potentiate the contractile response induced by acetylcholine and vasopressin. Conclusions: These observations suggest that β-sitosterol may be a useful modulator of the uterine motility during menstrual cycle, facilitating female fertility. [ABSTRACT FROM AUTHOR]

Background: Beta-sitosterol (β-sitosterol) is one of the several phytosterols widely studied for its potential to reduce benign prostatic hyperplasia and blood cholesterol levels. Objective: In the present study, the effects of β-sitosterol on spontaneous and agonist-induced contractions in in vitro nonpregnant human uterus with respect to prostaglandin E2 (PGE2) were investigated. Materials and Methods: Myometrial strips, measuring approximately 15 mm × 4 mm × 2 mm, were attained from hysterectomy samples of premenopausal women. Longitudinal muscle strips were mounted on tissue baths, under physiological conditions, to measure their isometric contraction. The effects of cumulative amounts of β-sitosterol on spontaneous motility in the absence and presence of prazosin, atropine, fulvestran, indomethacin, or ethylenediaminetetraacetic acid (EDTA), and on agonist-induced motor activity, were examined. Results: On strips in the follicular phase, both β-sitosterol (1-100 μg/ml) and PGE2 (0.1-10 μg/ml) increase, in a concentration-dependent manner, muscular basic tonus and amplitude and frequency of spontaneous uterine contractions; whereas on strips obtained during periovulatory phase, β-sitosterol and PGE2 cause inhibition of uterine motility. For contractile response, the effective concentrations (EC50) were 47.8 μg/ml and 5.19 μg/ml, respectively. Unlike indomethacin, the tissue pretreatment with prazosin, fulvestran, atropine, or ethylenediaminetetraacetic acid did not affect the contractile uterine responses to β-sitosterol. Furthermore, the β-sitosterol was able to potentiate the contractile response induced by acetylcholine and vasopressin. Conclusions: These observations suggest that β-sitosterol may be a useful modulator of the uterine motility during menstrual cycle, facilitating female fertility. [ABSTRACT FROM AUTHOR]

The objective of this in vitro study was to evaluate and compare the effects of scopolamine butylbromide (Spasmolax ® ) on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. The procedures were carried out in isolated organ bath. Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 5-min intervals starting 5 min before treatment until 10 min after treatment (5-min after xylazine administration and 5-min after scopolamine butylbromide addition). The results suggest that scopolamine butylbromide might decrease the tonic effect induced by xylazine on bovine pregnant uteri from 0-30 days to 240–270 days. [ABSTRACT FROM AUTHOR]

The assessment of uterine contractions is important in clinical decision-making, but the precise role for appraising contractions remains controversial. Four clinical approaches to assessing contractions are available: manual palpation; intrauterine pressure determination; external tocodynamometry; and electrohysterography. Palpation is inexpensive and harmless but requires the constant bedside presence of a trained observer. Intrauterine pressure measurement is considered the most sensitive and specific technique, and has become the standard by which other methods are judged; however, its quantitative measurements are not always precise or reproducible. Moreover, the availability of intrauterine pressure measurements does not seem to improve maternal or neonatal outcomes in most situations. External tocodynamometry is the most widely used technique. It is easy to apply and provides reasonably accurate information about the frequency and duration of contractions, but not their amplitude. It can require frequent adjustment during labor and might not work well in patients who are obese. Electrohysterography is a recently available noninvasive technology that detects uterine electrical activity using electrodes placed on the mother's abdominal wall. This approach is at least as reliable and accurate as tocodynamometry. [ABSTRACT FROM AUTHOR]

KIR7.1, an inwardly rectifying K+ channel, plays a critical role in regulating uterine excitability during pregnancy and has been suggested as a potential new target for the treatment of conditions arising from dysfunctional uterine contractility, for example, atonic postpartum hemorrhage. The aim of this study was to investigate the effects of the selective KIR7.1 blocker, VU590, on both spontaneous and agonist-stimulated contractions of human pregnant myometrium in vitro. At a concentration of 20 µmol/L, VU590 significantly increased the mean contractile force and the frequency of spontaneous contractions (P < 0.05) when compared to vehicle-treated tissues. However, there was a significant (P < 0.0001) monoexponential decay in amplitude with time of exposure. When VU590 was coadministered with EC50 concentration of the uterotonics oxytocin, ergometrine, or carboprost, the only significant changes were an immediate decrease in the amplitude of oxytocin- and carboprost-induced contractions and a delayed reduction in amplitude and an increase in the frequency of ergometrine-induced contractions. Amplitude to all 3 agents in the presence of VU590 showed a monoexponential decay with time of exposure (P < 0.0001). We conclude that VU590 modifies the contractility of pregnant human myometrium in support of a role for KIR7.1 in regulating that process. However, VU590 in vitro does not produce the types of contraction, either alone or in combination with other uterine stimulants that would suggest its usefulness as a first- or second-line clinical uterotonic agent. [ABSTRACT FROM AUTHOR]

Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4–19 years; body weight 405–530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality. After euthanasia, one uterine tissue sample was collected for histological evaluation and four full-thickness uterine tissue strips (10–12 mm × 2 mm), two parallel to each muscle layer, were excised for in-vitro contractility evaluation. Strips were suspended in tissue chambers containing Krebs–Henseleit solution, with continuous aeration (95% O 2 –5% CO 2 ; pH 7.4) at 37 °C. After equilibration, spontaneous contractility was recorded (pre-treatment) and strips excised in each direction were randomly allocated to each of two groups: 1) SNAP (S-nitroso-N-acetylpenicillamine, an NO donor); or 2) NAP (N-acetyl- d -penicillamine, vehicle and time-matched control). These were treated at 15 min intervals with increasing concentrations (10 −7 M to 10 −3 M) of SNAP and NAP, respectively. Contractility data was recorded throughout the experiment. An interaction effect of group-by-concentration was observed (P < 0.0001). The mean contractility after treatment with 10 −4 M and 10 −3 M SNAP were significantly lower than the pre-treatment contractility and the mean contractility after treatment with lower SNAP concentrations. In contrast, contractility did not change significantly in the NAP treated controls. The effect of treatment on uterine contractility was not influenced by age or weight of the mare, stage of estrous cycle, uterine histology grade, or muscle layer. Secondary findings included significant main effects of stage of estrous cycle (increased contractility in estrus compared to diestrus), uterine histology grade (decreased contractility in grade IIB compared to grade I) and age (decreased contractility in mares aged > 8 years compared to mares aged ≤ 8 years). In conclusion, results of this study indicate that NO has a dose-dependent inhibitory effect on spontaneous uterine contractility irrespective of the muscle layer in the mare. [ABSTRACT FROM AUTHOR]

Background: The mechanisms for myometrial inhibition are still being investigated Aim: To examine mechanisms of progesterone (P4) inhibition of uterine contractility. Methods: Prospective study Tertiary care center at St. Joseph’s Hospital and at Maricopa Hospital, Phoenix, AZ and research center in Arizona, USA. During 2010-2011, 24 women given birth by cesarean section. Uterine tissues from women (n=24) at term were suspended in organ chambers and exposed to various agents. Contractility was registered and compared before and after addition of agents. Tissues were treated with P4 alone, a progestin (R5020) with low affinity to the progesterone membrane receptor (mPR), or a non-sex steroid (cholesterol). Other tissues were pretreated with inhibitors of adenylate cyclase (SQ 22536), phosphodiesterase (rolipram), nitric oxide (NO) synthases (L-NAME) or a nuclear P4 receptor antagonist (mifepristone, MIF), followed by P4. Data were analyzed by ANOVA. Results: P4 (P0.05) inhibitory effects. P4 inhibition is not blocked by MIF, SQ, ODQ, rolipram or L-NAME (P>0.05). Conclusions: P4 rapidly inhibits myometrial contractility by nongenomic mechanisms through action on mPR but not via cAMP, cGMP, or NO [Cukurova Med J 2013; 38(1.000): 92-102]