Uterine Motility Research Articles

The therapeutic mechanism of Curcumae Radix against primary dysmenorrea based on 5-HTR/Ca2+/MAPK and fatty acids metabolomics.

Background: Curcumae Radix (CW) is traditionally used to treat primary dysmenorrea (PD). However, the mechanisms of action of CW in the treatment of PD have not yet been comprehensively resolved. Objective: To investigate the therapeutic effects of CW on PD and its possible mechanisms of action. Methods: An isolated uterine spastic contraction model induced by oxytocin was constructed in an in vitro pharmacodynamic assay. An animal model of PD induced by combined estradiol benzoate and adrenaline hydrochloride-assisted stimulation was established. After oral administration of CW, a histopathological examination was performed and biochemical factor levels were measured to evaluate the therapeutic effect of CW on PD. The chemical compositions of the drug-containing serum and its metabolites were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Network pharmacology and serum untargeted metabolomics were used to predict the mechanism of CW treatment for PD, and the predicted results were validated by RT-qPCR, WB, and targeted fatty acid (FA) metabolism. Results: In vitro, CW can relax an isolated uterus by reducing uterine motility. In vivo, the results showed that CW attenuated histopathological damage in the uterus and regulated PGF2α, PGE2, β-EP, 5-HT, and Ca2+ levels in PD rats. A total of 66 compounds and their metabolites were identified in the drug-containing serum, and the metabolic pathways of these components mainly included hydrogenation and oxidation. Mechanistic studies showed that CW downregulated the expression of key genes in the 5-HTR/Ca2+/MAPK pathway, such as 5-HTR2A, IP3R, PKC, cALM, and ERK. Similarly, CW downregulated the expression of key proteins in the 5-HTR/Ca2+/MAPK pathway, such as p-ERK/ERK. Indirectly, it ameliorates the abnormal FA metabolism downstream of this signaling pathway in PD rats, especially the metabolism of arachidonic acid (AA). Conclusion: The development of PD may be associated with the inhibition of the 5-HTR/Ca2+/MAPK signaling pathway and FA metabolic pathways, providing a basis for the subsequent exploitation of CW.

Building a Co-ordinated Musculoskeletal System: The Plasticity of the Developing Skeleton in Response to Muscle Contractions.

The skeletal musculature and the cartilage, bone and other connective tissues of the skeleton are intimately co-ordinated. The shape, size and structure of each bone in the body is sculpted through dynamic physical stimuli generated by muscle contraction, from early development, with onset of the first embryo movements, and through repair and remodelling in later life. The importance of muscle movement during development is shown by congenital abnormalities where infants that experience reduced movement in the uterus present a sequence of skeletal issues including temporary brittle bones and joint dysplasia. A variety of animal models, utilising different immobilisation scenarios, have demonstrated the precise timing and events that are dependent on mechanical stimulation from movement. This chapter lays out the evidence for skeletal system dependence on muscle movement, gleaned largely from mouse and chick immobilised embryos, showing the many aspects of skeletal development affected. Effects are seen in joint development, ossification, the size and shape of skeletal rudiments and tendons, including compromised mechanical function. The enormous plasticity of the skeletal system in response to muscle contraction is a key factor in building a responsive, functional system. Insights from this work have implications for our understanding of morphological evolution, particularly the challenging concept of emergence of new structures. It is also providing insight for the potential of physical therapy for infants suffering the effects of reduced uterine movement and is enhancing our understanding of the cellular and molecular mechanisms involved in skeletal tissue differentiation, with potential for informing regenerative therapies.

Quantitative Ultrasound Measurement of Endometrial Waves in Adenomyosis Versus Women with Normal Uteri - the Waves Study

<h3>Study Objective</h3> Measurement and analysis of uterine contractions by quantitative 2D transvaginal ultrasound measurements in women with abnormal uteri due to adenomyosis versus women with normal uteri. <h3>Design</h3> Multi-centre prospective observational cohort study. <h3>Setting</h3> Outpatient gynaecology department of participating centres. <h3>Patients or Participants</h3> 29 women with adenomyosis with a natural menstrual cycle were compared to 70 women with normal uteri and regular menstrual cycles. Patients were included from September 2014 up to January 2022. <h3>Interventions</h3> Patients underwent a 4-minute 2D transvaginal ultrasound of the uterus in mid-sagittal section. Uterine motion analysis was implemented by a dedicated speckle tracking and strain analysis algorithm; with frequency, amplitude, coordination and velocity -related features extracted from the derived signals to characterise the uterine contractions. Measurements were carried out at different points of the menstrual cycle (menstrual, early follicular, periovulatory and early and late luteal phases. <h3>Measurements and Main Results</h3> Results differed most significantly between groups in the periovulatory phase, with women with adenomyosis showing lower frequency (1.44 vs. 1.79 contractions/minute, p=0.025), higher amplitude (0.09 vs. 0.04, p=0.000) and lower velocity of uterine contractions (0.62 vs. 0.83 mm/sec, p=0.0008). In the menstrual phase, women with adenomyosis showed a trend toward higher contraction frequency (1.37 vs, 1.33 contractions/minute, p=0.592), amplitude (0.05 vs. 0.04, p=0.259) and velocity (0.72 vs. 0.67, p=0.456). Across all phases, women with adenomyosis showed a trend towards reduced contraction coordination (0.23-0.34 vs. 0.15-0.26). This being statistically significant in the late luteal phase (p=0.018). <h3>Conclusion</h3> Our results confirm differences in uterine movement in abnormal versus healthy uteri. This could add to the aetiological understanding of clinical symptoms of these conditions (i.e. dysmenorrhoea or infertility). The notable difference between groups regarding coordination identifies this feature as a potential prognostic or therapeutic marker. Further research in women with (other) benign uterine disorders will hopefully lead to a better understanding of the clinical implications of abnormal uterine contractility.

Clinical practice guidelines for endometriosis in Japan (The 3rd edition).

Clinical practice guidelines for endometriosis in Japan (The 3rd edition).

Effect of different acupuncture and moxibustion methods on uterine contraction and microcirculation in cold congealing dysmenorrhea rats

To observe and compare the effects of different acupuncture and moxibustionmethods at "San-yinjiao" (SP6) on uterine contraction and microcirculation in cold congealing dysmenorrhea rats, so as to explore its mechanism underlying treatment of dysmenorrhea. A total of 140 female SD rats were randomly divided into normal control, mo-del, perpendicular needling, transverse needling and moxibustion groups, with 28 rats in each group. The cold congealing dysme-norrhea rat model was prepared by exposure in a freezer (25 ℃) for 4 h, once daily for 5 days, and subcutaneous injection of estradiol benzoate (once daily for 10 days) and intra-abdominal injection of oxytocin (once). For rats in three intervention groups, acupuncture needles were inserted into bilateral SP6 perpendicularly or transversely to a depth of 4~5 mm and retained for 20 min, or moxibustion was applied to SP6 for 20 min. The uterine contraction degree and the uterine microcirculation were recorded. The expression levels of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein 70 (HSP70) in local tissues of SP6 area were detected by immunohistochemistry. The expression levels of μopioid receptor and endothelin 1 (ET1) mRNA in the uterus were assessed by quantitative real time-PCR. After modeling and compared with the normal control group, the number and peak-to-peak values of uterine contraction waves, and uterine motility were significantly increased (P<0.01,P<0.05), while the speed of blood flow in the microvessels was slowed down (P<0.01), diameters of the uterine microvessels and capillaries (cap) shrank obviously (P<0.01) in the model group. After the intervention, all indexes of uterine contraction and microcirculation were improved in three intervention groups (P<0.01, P<0.05), while transverse needling and moxibustion showed better effects compared to perpendicular needling (P<0.05, P<0.01). The expression of TRPV1 and HSP70 in SP 6 area had no significant changes (P>0.05), while the uterine μopioid receptor mRNA expression decreased (P<0.01), and ET1 mRNA expression increased (P<0.01) in the model group relevant to the normal control group. Following the intervention, the expression levels of TRPV1 and HSP70 in SP6 area were increased (P<0.05, P<0.01), and expression levels of uterine μopioid receptor mRNA increased (P<0.05, P<0.01) and uterine ET1 mRNA decreased (P<0.05, P<0.01) in the three intervention groups. The effect of moxibustion was considerably better than those of two acupuncture groups in up-regulating TRPV1 expression (P<0.05). Both transverse needling and moxibustion showed better effects of down-regulating uterine ET1 mRNA expression than perpendicular needling (P<0.01). Transverse needling and moxibustion at SP6 have a better effect of relieving ute-rine contraction and improving uterine microcirculation than perpendicular needling, which may be related to their effects in up-re-gulating the expression of TRPV1 and HSP70 in SP6 area, thereby modulating the mRNA expression of μ opioid receptor and ET1 in uterine tissue.

ВЛИЯНИЕ НАСТОЙКИ БЕЛОЙ ЧЕМЕРИЦЫ НА МИОТРОПНУЮ ФУНКЦИЮ МАТКИ КОРОВ ПОСЛЕ ОТЕЛА

The article presents the results of hysterographic studies on three groups of cows 6 hours after calving, which were injected intrauterinely, single, at a dose of 100 ml, 100 ml of a mixture consisting of 10% tincture of white hellebore and distilled water. For the cows of the first experimental group, a mixture with a ratio of white hellebore tincture and water of 1:99 was used; the second experimental group - 3:97; third - 6:94. Hysterographic studies of the cows of the first experimental group showed that if before the intrauterine administration of the medicine the contraction index was 54477.22 * 123.12 Pa, then after 20 minutes it increased to 208567.52 * 533.25 Pa or by 382.85%. Then, a downward trend was noted in the index of contraction activity of the uterine myometrium: after 60 minutes to 124844.26 * 876.87 Pa (by 167.06%), 180 minutes - to 48634.53 * 365.57 Pa (by 428.85%), 360 minutes - up to 38248.59 * 175.41Pa (by 545.29%). In cows of the second experimental group, uterine contractions had a high amplitude, mostly tower-shaped. The waves of uterine contractions were longer than in spontaneous contraction of the myometrium, and the pauses were shorter. After 180 and 360 minutes, the rhythm and amplitude of uterine contractions almost corresponded to those before the use of the mixture. In cows of the third experimental group, the index of contraction activity of the myometrium before the administration of the mixture was 53543.17 * 211.32 Pa and increased 20 minutes after stimulation by 713.90%, and after 60 minutes it decreased by 339.89%. Then, after 180 minutes, its decrease was noted by 1028.72 and 1394.41%, respectively. The most optimal for stimulating uterine motility in cows during retention of the placenta can be considered a mixture consisting of 3 parts of a 10% tincture of white hellebore and 97 parts of distilled water.

Assessment of Correlation between Amniotic Fluid Index (AFI) and Feto-maternal Outcomes of In-term Pregnancies

Background: Amniotic fluid plays a crucial role in providing basic life support to the fetus. This clear, slightly yellowish liquid that surrounds the fetus is helpful in the development of fetal systems by providing thermally controlled and a non-restricted sterile environment for fetal growth. During labour, amniotic fluid helps in providing an adequate cushion for umbilical cord. It is this mechanical function of the cushion which aids in preventing compression of cord in-between fetus and uterine wall during uterine contractions and fetal movements. Therefore, helps to prevent fetal distress. It protects fetus from any kind of injury and helps in preventing infection by its bacteriostatic properties. This study aims to estimate the effect of decreased amniotic fluid index (AFI) on maternal and fetal outcomes in term pregnancy.&#x0D; Materials and Methods: This will be a Prospective cross sectional observational study conducted in OBGY dept. of AVBRH, Wardha. Pregnant women will be enrolled and divided into 3 groups as per Amniotic Fluid Index. Group A with low amniotic fluid index (AFI&lt; 5 cm) Group B with borderline amniotic fluid index (AFI&gt;5cm and &lt;8cm)and Group C with normal amniotic fluid index (AFI 8cm-24cm). Data will be collected, analysed and compared between the groups in terms of the ultrasonographic findings and feto-maternal outcomes of in term pregnancy.&#x0D; Expected Results: Significant correlation is expected between AFI and feto-maternal outcomes.&#x0D; Conclusion: Unexpected adverse outcomes can be minimized by estimation of AFI and timely antepartum treatment in mothers with decreased AFI.

O-058 The impact of endometriosis on fertility treatment

Abstract Abstract text Endometriosis can affect natural fertility by distorting pelvic anatomy and by causing local pelvic inflammation that affects the quality of the oocytes, the function of the tubes and the sperm capacity to fertilize. Two approaches can be foreseen, either removing the disease with the aim of restoring normality (surgery) or overcoming the disease by retrieving oocytes in the ovary and allowing their fertilization in in vitro conditions (IVF). Both therapeutic approaches seem rational and wise. However, despite this apparently simple clinical scenario, management of endometriosis-related infertility has engendered long-lasting and burning debates over the last two decades and, to date, no consensus has been reached. Robust scientific evidence is scant, actually limited to the demonstration that laparoscopy modestly increases the chance of natural conception. In this debate, it is noteworthy that chances of pregnancy do not represent the unique stake. Other factors can play a role and deserves consideration. Considering the choice of fertility treatment, he most relevant are the following: 1) the impact of ovarian endometriomas and their removal on ovarian responsiveness, 2) the impact of endometriomas and endometriosis in general on oocytes quality, 3) the additional risks of oocytes retrieval in the presence of endometriosis (infections in particular) 4) the detrimental effects of endometriosis-related hydrosalpinx, 5) the impact of endometriosis on uterine motility and endometrial receptivity, 5) the confounding effect of endometriosis-associated adenomyosis. Unfortunately, for the vast majority of these concerns, evidence is not definite and physicians have to take decisions based on their clinical commonsense.

A Pregnancy Prediction System based on Uterine Peristalsis from Ultrasonic Images

In infertility treatment, it is required to improve a success rate of the treatment. A purpose of this study is to develop a prediction system for pregnancy outcomes using ultrasonic images. In infertility treatment, it is typical to evaluate the endometrial shape by using ultrasonic images. The convolutional neural network (CNN) system developed in the current study predicted pregnancy outcome by velocity information. The velocity information has a movement feature of uterine. It is known that a uterine movement is deep related to infertility. Experiments compared the velocity-based and shape-based systems. The shape-based systems predict the optimal uterine features for pregnancy success based on endometrial shape by inputting original ultrasonic images to CNN model. The current findings revealed that the velocity-based system provided similar accuracy to the shape-based systems. However, the output of the velocity-based system, the area under curve (AUC) for the receiver operating characteristic (ROC) curve, provided a higher value than the shape-based systems. The AUC values of the shape-based and velocity-based systems were 0.65, and 0.72, respectively. These results showed that the analysis of the velocity of uterine movements was effective for pregnancy outcome prediction. Previous clinical evaluation did not target the uterine movement but only the endometrial shape. Therefore, this study has revealed a new treatment approach for infertility.

Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments promotes uterine contractility

To investigate the effect of manual acupuncture stimulation of acupoints at different spinal nerve segments on uterine motility and the complicated adrenergic and cholinergic receptors. Eighteen adult non-pregnant SD rats were used in the present study. The contractive activities of the uterus were measured by using a pressure transducer which was connected to an inserted water-filled balloon in the uterus via a PE tube at one end and an amplifier at the other end. Manual acupuncture needle was applied to "Zigong"(EX-CA1),"Huiyin" (CV1), "Xuehai "(SP10) and "Taichong "(LR3) acupoints located at the same or adjacent spinal nerve segments of the uterus, and to "Neiguan" (PC6) situated at the distant spinal nerve segment at about 2 Hz for 1 min, followed by observing changes of the uterine contractility. After acupuncture, α-adrenoceptor antagonist phentolamine (0.5 mg/kg, n=9) or cholinergic muscarinic (M) receptor antagonist atropine (0.5 mg/kg，n=9) was given to the rats of different acupoints respectively through tail vein, followed by observing changes of the uterine automatic systolic pressure difference (value of systolic pressure peak minuses the trough value) and frequency after manual acupuncture stimulation as well as after blocking the activities of α-adrenoceptors and M receptors, separately. After acupuncture stimulation of EX-CA1, CV1, SP10 and LR3, but not PC6, the systolic pressure difference and frequency of the uterus were signi-ficantly increased (P<0.05,P<0.001, P<0.01). Following intravenous injection of phentolamine, both the systolic pressure difference and frequency had no marked changes after acupuncture at the 5 acupoints (P>0.05). After intravenous injection of atropine, the uterine systolic pressure difference and frequency were markedly decreased compared with the basic values before acupuncture stimulation (P<0.001), but had no obvious changes after acupuncture at the 5 acupoints at both the same and distant spinal segments to the uterus (P>0.05). Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments can promote the contractility of uterus in normal rats, which is realized by activating both α-adrenoceptor and cholinergic M receptors.

ATOSIBAN AND BARUSIBAN IMPROVED IMPAIRED ENDOMETRIAL BLOOD FLOW IN PREGNANT RABBITS

Despite considerable success in generating human blastocytes with artificial reproductive technologies, embryo implantation remains a challenge for unclear reasons. Excessive uterine movements may cause implantation failure while atosiban (ATO), a mixed vasopressin (VP) V1A/oxytocin (OT) receptor antagonist, is used off-label to normalize uterine movements. In addition to inflammation or iatrogenic factors, poor perfusion can contribute to low implantation rates. It is hypothesized that elevating the uterine blood perfusion may increase the quality of the uterine mucosa and thus implantation success.

A Uterine Motion Classification in MRI Data for Female Infertility.

The purpose of this study was to classify complicated uterine movements obtained by MRI scanner and investigate the relationship between uterine peristalsis and female infertility. Uterine movements are classified into six fundamental movements by their motility form and directions. Computer simulation of the uterine movements is performed. Comparison results between the real MRI images and the simulated images showed that any five in our dataset uterine movement was successfully reproduced by a combination of these six fundamental movements. The point and surface vibration model appropriately mimicked the movements with the propagation velocity of 0.68 [mm/sec]. By analyzing six fundamental movements using data from 26 MRI scans, it was found that two fundamental movements were identified as candidate factors for female infertility.

Ex Vivo Method for Assessing the Mouse Reproductive Tract Spontaneous Motility and a MATLAB-based Uterus Motion Tracking Algorithm for Data Analysis.

Dysmenorrhea, or painful cramping, is the most common symptom associated with menses in females and its severity can hinder women's everyday lives. Here, we present an easy and inexpensive method that would be instrumental for testing new drugs decreasing uterine contractility. This method utilizes the unique ability of the entire mouse reproductive tract to exhibit spontaneous motility when maintained ex vivo in a Petri dish containing oxygenated Krebs buffer. This spontaneous motility resembles the wave-like myometrial activity of the human uterus, referred to as endometrial waves. To demonstrate the effectiveness of the method, we employed a well-known uterine relaxant drug, epinephrine. We demonstrate that the spontaneous motility of the entire mouse reproductive tract can be quickly and reversibly inhibited by 1 µM epinephrine in this Petri dish model. Documenting the changes of uterine motility can be easily done using an ordinary smart phone or a sophisticated digital camera. We developed a MATLAB-based algorithm allowing motion tracking to quantify spontaneous uterine motility changes by measuring the rate of uterine horn movements. A major advantage of this ex vivo approach is that the reproductive tract remains intact throughout the entire experiment, preserving all intrinsic intrauterine cellular interactions. The major limitation of this approach is that up to 10-20% of uteri may exhibit no spontaneous motility. Thus far, this is the first quantitative ex vivo method for assessing spontaneous uterine motility in a Petri dish model.

The role of cine MR imaging in the assessment of uterine function.

To review the literature on uterine contraction and to highlight magnetic resonance imaging using the cine technique as a useful method to evaluate these movements. The literature research on PubMed database was done up to February 2019 with restriction to English language about articles regarding uterine peristalsis and cine MR. Infertility is a common clinical problem and a source of frustration for those who want to have children. Uterine movements are crucial elements in respect of successful conception, implantation, and the development of a healthy pregnancy. It is known that the direction and frequency of uterine peristalsis are closely related to the different phases of the menstrual cycle, and that changes in its activity may interfere with reproduction. One condition that has been linked with infertility by several studies is dysfunctional uterine contractility. Magnetic resonance imaging, using the cine technique, has been shown to be a useful tool in the evaluation of these movements, allowing the identification of patients with some type of dysfunction and establish strategies to increase pregnancy rates. Cine MR is an excellent imaging method for the evaluation of uterine peristalsis and identification of dysfunctional contractions.

Effects of the Combined Therapy of Acupuncture with Herbal Drugs on Male &amp;amp; Female Immune Infertility at Puducherry, South India

Acupuncture has been used to treat infertility extensively, including ovulatory dysfunction, in vitro fertilization and embryo transfer (IVF-ET), and male infertility. This review summarizes the recent studies which investigated the role of acupuncture in infertility. Firstly, acupuncture may improve ovulation by modulating the central and peripheral nervous systems, the neuroendocrine and endocrine systems, the ovarian blood flow, and metabolism. Secondly, acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of fertility.Soto study the clinical effects of the combined therapy of acupuncture with herbal drugs on male and female immune infertility, we have choosen 100 patients with infertility and given the combined therapy, (acupuncture herbal-drug treatment) .Thecontrolgroupwas treated with oral prednisone. The results showed that the total effective rate in the combined drug treatment acupuncture- herbal drug group was 90%; showing a statistically significant difference (P<0.05).The combined therapy of acupuncture with herbal drugs has definite therapeutic effects on male and female immune infertility.

Proteomic profile of histotroph during early embryo development in mares

There is a complex cascade involving proteins during early embryo development and maternal recognition, which is very important for maintenance of a conceptus. The aim of this study was to compare proteomic profile of uterine fluid after ovulation in pregnant and cyclic mares. In the first cycle, samples of uterine fluid of 30 cyclic mares were collected on days 7 (n = 10), 10 (n = 10) and 13 (n = 10) post ovulation and constituted the Cyclic group. In the second cycle, the same mares were bred to a fertile stallion. At days 7, 10 and 13 uterine fluid samples were collected. Immediately after sample collection, the mare's uteri were flushed, and those with an embryo recovered were assigned to the Pregnant group. Of the 30 mares flushed embryos were recovered from 6 mares on day 7, 6 on day 10 and 6 on day 13. Samples from the mares without embryo recovery were excluded from both groups. The uterine fluid samples were processed by two-dimensional electrophoresis technique followed by matrix assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry for the identification of relevant protein spots. From a total of 677 detected spots 19 were identified, 13 more abundant in Pregnant group and 6 in Cyclic group. In summary, pregnant and cyclic mares showed proteins with different abundance. Identified proteins were related to the transport of lipids through the embryo capsule, uterine motility, ATP generation, maternal immunological tolerance, cell proliferation, differentiation, metabolism and angiogenesis. Changes in the proteomic profile of uterine fluid during early embryo development in mares were related with the conceptus presence, suggesting that these alterations may be important for conceptus development and maternal recognition of pregnancy.

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. – An in vitro and in vivo study

BackgroundAnanas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions. PurposeThe aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4. Materials and methodsOrgan bath studies were employed to compare the stimulatory effect of F4 in non and late pregnant uterine tissue followed by isolation of protein from late pregnant uterine tissue for the western blot analysis. The PhysioTel transmitter was implanted in pregnant SD rats to measure the changes in intrauterine pressure (IUP). Analyses of the crude extract and active principle in F4 was performed using LC-HRMS. ResultsRipe F4 in a similar manner as serotonin produced a greater stimulatory response in late pregnant than non-pregnant uterine tissue without significant change in potency; ripe F4 also increased ERK phosphorylation which eventually led to a significant increase of the final product, MMP-13. In pregnant rats (E18), oral ripe F4 (1.5 g.100 g−1 body weight) and ergometrine (1 mg) did not stimulate the uterine contraction probably due to the low level of estradiol and as a consequence low 5-HT receptors at the time of administration. In contrast, in postpartum rats, oral administration of F4 and ergometrine produced a significant increase in maximal IUP to 4.3 and 4.9 folds of basal IUP respectively. Contrary to the folklore use, unripe F4 did not stimulate the uterine activity during pregnancy and postpartum. Bioassay guided fractionation identified serotonin as a major bioactive compound in ripe F4. ConclusionsOur data clearly indicate that the uterotonic effect of ripe F4 is mediated via the serotonergic pathway and suggest that serotonin rich diet may increase the peripheral serotonin and implicate in diverse physiological functions, including uterine motility.

SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial.

SR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients. This trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas' pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety. After oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas' pouch, limitation of uterine movement compared with the baseline values. The present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time.

Effects of beta-sitosterol on isolated human non-pregnant uterus in comparison to prostaglandin E2

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 PGE2cause 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.

Scopolamine butylbromide decreases the xylazine-mediated contractility in bovine pregnant uteri

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.