Myometrial Contractions Research Articles

Cooperation of aquaporin 5 and the adrenergic system in the initiation of birth in rat model

Aquaporins (AQPs) are involved in the process of implantation, regulate myometrial contractions and cervical ripening, and maintain appropriate placental functioning. The molecular mechanism of these functions is not fully understood. Our study aimed to investigate the physiological significance of AQP5 during pregnancy and to determine the cooperation between the adrenergic system and the AQP5 in uterine contraction in the late-pregnant rat uterus.After administering AQP5 siRNA intraperitoneally to Sprague-Dawley rats, the length of the gestational period was determined and the changes in uterine contractions were measured in an isolated organ bath system. Pharmacological influence on AQP5 expression and uterine contraction was investigated by treatment with terbutaline (10 mg/kg, subcutaneously) and doxazosin (5 mg/kg, orally) in vivo; and mercuric chloride (HgCl2), in vitro. Moreover, the levels of cAMP response element binding protein (CREB) were measured in the uterus by an ELISA kit.The gestational period became shorter, AQP5 expression significantly decreased and rat uterus contraction increased after AQP5 siRNA treatment compared to the control. Treatment with terbutaline significantly increased AQP5 mRNA and protein expression after 30 min and continuously reduced it until 90 min, whereas doxazosin treatment did not significantly alter AQP5 expression. Treatment with the AQP5 antagonist HgCl2 increased spontaneous uterus contraction and decreased norepinephrine-induced uterus contraction with decreasing AQP5 expression in pregnant rat uterus. Moreover, the tocolytic effect through the adrenergic system was amplified in the presence of an AQP5 antagonist, presumably via the changes in cAMP level.In conclusion, our findings elucidate the collaborative role of aquaporin 5 (AQP5) and adrenergic systems in the regulation of uterine contractions in late-pregnant rats. Our findings suggest this may be a good starting point for developing a new tocolytic therapy.

Haplotype-resolved assembly of the mule duck genome using high-fidelity sequencing technology.

Mule duck is vitally important to the production of global duck meat. Here, we present two high-quality haplotypes of a female mule duck (haplotype 1 (H1):1.28 Gb, haplotype 2 (H2): 1.40 Gb). The continuity (H1: contig N50 = 14.90 Mb, H2: contig N50 = 15.70 Mb) and completeness (BUSCO: H1 = 96.9%, H2 = 97.3%) are substantially better than those of other duck genomes. We detected the structural variations (SVs) in H1 and H2. We observed a positive correlation between autosome length and the number of SVs. Z chromosome was some deficient in deletions and insertions, but W chromosome was some excessive. A total of 1,451 genes were haplotype specific expression (HSEs). Among them, 737 specifically expressed in H1, and 714 specifically expressed in H2. We found that H1 and H2 HSEs tended to be involved in similar biological processes, such as myometrial relaxation and contraction pathways, muscle structure development and phosphorylation. Our haplotype-resolved genome assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in mule duck.

Müllerian anomalies and endometriosis as potential explanatory models for the retrograde menstruation/implantation and the embryonic remnants/celomic metaplasia pathogenic theories: a systematic review and meta-analysis.

Does endometriosis prevalence differ in patients with obstructive Müllerian anomalies (OMA) versus those with nonobstructive Müllerian anomalies (NOMA), and in patients with NOMA versus those without Müllerian anomalies? The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without Müllerian anomalies. The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without Müllerian anomalies would support the embryonic remnants/celomic metaplasia hypothesis. This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword 'endometriosis' in combination with 'Müllerian anomalies', 'obstructive Müllerian anomalies', 'female genital malformations', 'retrograde menstruation', 'infertility', 'pelvic pain', and 'classification'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used. Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without Müllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with Müllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete Müllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36-58%) in patients with OMA, and 19% (95% CI, 15-24%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54-8.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20-27%), and that in patients without Müllerian anomalies was 21% (95% CI, 20-22%), with a common OR of 0.95 (95% CI, 0.57-1.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons. Some NOMA subtypes may create a partial obstacle to menstrual efflux and/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without Müllerian anomalies. The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors. No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. N/A.

Bryophyllum pinnatum Inhibits Oxytocin and Vasopressin Signaling in Myometrial Cells.

The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT-C3, and cell lines expressing recombinant human OT and V1A receptors.We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT-C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V1A receptor-mediated signals with a similar potency (IC50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT-C3 cells.In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Extracellular acidification increases uterine contraction in pregnant mouse by increasing intracellular calcium.

As uterine extracellular pH decreases during the ischemic conditions of labor, but its effects on myometrial contraction are largely unknown, there is a need to elucidate its physiological effects and mechanisms of action. Furthermore, it is not known if any of the effects of extracellular acidification are affected by pregnancy, thus we also determined how gestation affects the response to acidification. Nonpregnant, mid-, and term-pregnant myometrial strips were obtained from humanely killed mice. Contractions were recorded under spontaneous, depolarized, and oxytocin-stimulated conditions. The extracellular pH of the perfusate was changed from 7.4 to 6.9 or 7.9 in HEPES-buffered physiological saline. Intracellular pH was measured using SNARF, and intracellular calcium was measured using Indo-1. Statistical differences were tested using the appropriate t-test. Extracellular acidification significantly increased the frequency and amplitude of spontaneous contractions in pregnant, but not nonpregnant, myometrium, whereas alkalinization decreased contractions. Intracellular acidification, via Na-butyrate, transiently increased force in pregnant tissue. Intracellular pH was gradually acidified when extracellular pH was acidified, but extracellular acidification increased contractility before any significant change in intracellular pH. If myometrial force was driven by oxytocin or high-K depolarization, then extracellular pH did not further increase force. Intracellular calcium changes mirrored those of force in the spontaneously contracting pregnant myometrium, and if calcium entry was prevented by nifedipine, extracellular acidification could not induce a rise in force. Extracellular acidification increases excitability, calcium entry, and thus force in pregnant mouse myometrium, and this may contribute to increasing contractions during labor when ischemic conditions and acidemia occur.

Primary dysmenorrhea: pathophysiology, improvement of diagnostic and treatment possibilities

Primary dysmenorrhea is one of the types of gynecological pathology, the frequency of which is 45-53% in girls and young women aged 13 to 45 years, which is not given enough attention in diagnosis and treatment.The pathogenesis takes into account the increased secretion of prostaglandins F2α and E2 in the period from the beginning of pregnancy to birth, which cause pelvic pain.The diagnosis is based on the patient's history, symptoms, examination, the treatment is aimed at improving the quality of life by prescribing nonsteroidal anti-inflammatory drugs, hormonal contraceptives and the use of non-medicinal means. Purpose: to specify some links in the pathogenesis of primary dysmenorrhea and, taking into account its multicomponent nature, to evaluate the effectiveness of the proposed treatment. Under observation there were 68 women who were divided into 2 groups: 34 women with primary dysme­norrhea (main group) and 34 healthy women (control group).The diagnosis of primary dysmenorrhea was established on the basis of complaints of patients about painful menstruation and accompanying symptoms during consultations with a gynecologist and endocrinologist.Treatment of patients in the main group was carried out with the drug, which includes Vitex agnus castus L, indinol-3-carbinol, 3,3-diindolyl-methane, extract of passionflower, California Eschscholzia. In women with typical symptoms, dysmenorrhea can be diagnosed on the basis of medical information without physical pelvic examination, empirical treatment should be initiated, including nonsteroidal anti-inflammatory drugs and/or oral contraceptives, because it is a functional condition resulting from an imbalance in the hormonal regulation of myometrial contraction. As a result of the proposed treatment, pain disappeared completely in 70% of patients (23/34), as well as vegetative-vascular (from 18 to 2% of patients), vegetative (from 10 to 1% of patients), metabolic and endocrine disorders (from 15 to 2% female patients), disorders of the emotional and mental sphere (from 25 to 10% of patients). Improvement in quality of life was noted by 80% (26/34) of patients, improvement in working capacity – by 70% (23/34) of patients, after 2 months – by 95% (31/34) and 85% (28/34), respectively, after 3 months all examined patients with primary dysmenorrhea noted an improvement in the quality of life and an increase in work capacity. Sexually active women with symptoms of inflammatory processes of the genital tract, severe dysmenorrhea should undergo pelvic examination. In view of safety and high therapeutic efficiency, the drug based on Vitex agnus castus can be offered for the treatment over the period lasting at least for3 months for girls and young women aged 13 to 45 years with primary dysmenorrhea.

In vitro inhibition of uterine contractions using electrospun nanofibers loaded with nifedipine and ML7.

To formulate a nanofiber-based controlled drug delivery system that could be effective in preventing uterine contractions and can be used for the treatment of preterm labor. We utilized uterine tissue samples obtained from ten pregnant women who underwent cesarean section at term to investigate the effect of nanofibers on spontaneous and induced myometrial contractions. We prepared nifedipine and ML7-loaded nanofibers using the electrospinning method with Poly(D,L-lactide-co-glycolide) (PLGA) polymer, resulted in seven groups of nanofibers, including a control group. Group I served as the control, Group II was non-drug loaded nanofiber, Group III was nifedipine (10-5 M) loaded nanofiber, Group IV was ML7 (3x10-5 M) loaded nanofiber, Group V was ML7 (3x10-5 M) and nifedipine (10-5 M) nanofiber, Group VI was ML7 (3x10-5 M) and nifedipine (3x10-5 M) nanofiber, and Group VII was ML7 (3x10-5 M) and nifedipine (10-4 M) nanofiber. To evaluate the contractile response, the nanofibers loaded with different doses of ML7 and nifedipine were applied onto the tissue strips, and in vitro organ bath experiments were performed. Full-thickness uterine samples were cleared of the serosa and surrounding tissues, and eight strips (3x10 mm) were prepared from each sample. The seven different nanofiber formulations were gently placed and sutured onto the strips, with one strip always kept as the time control. We recorded spontaneous, KCl-induced, and stimulated cumulative oxytocin-induced contractions from all samples in all groups. After completing all experiments, the viability of the strips was checked, and weight measurement was recorded. The administration of drug-loaded polymers resulted in a significant decrease in both the frequency and intensity of spontaneous and induced contractions in all groups (p<0.01). No significant difference was observed between the control group and the non-drug-loaded nanofiber group in post hoc analysis (p=0.704). In terms of amplitude and frequency of contractions, the most significant decrease was observed in group VII at cumulative oxytocin doses compared to the control and non-drug-loaded nanofiber groups (p<0.05). Moreover, group VI also showed a significant decrease in contraction intensity and frequency compared to the control and non-drug-loaded nanofiber groups (p<0.05). While the use of nifedipine and/or ML7-loaded nanofibers decreased both intensity and frequency of contraction, this attenuation was not significant compared to the control and empty polymer groups. However, a more significant inhibition was observed when ML7 was used with nifedipine at doses of 3x10-5 M and 10-4 M. The results indicate that human uterine contractions can be inhibited using calcium channel blocker (nifedipine) and myosin light chain kinase inhibitor (ML7) loaded nanofibers in uterine tissue strips. These results strongly suggested the potential for the development of locally effective and safe controlled drug release systems to prevent premature birth.

The Relationship between the Prevalence of Cesarean Sections and Progesterone (Duphaston) Usage during Pregnancy

Background: Progesterone plays a crucial part in ovulation, implantation, and pregnancy, among other reproductive processes.This is related to progesterone's role in controlling cyclical changes in decidualization and proliferation, which regulate uterine function during the menstrual cycle. Progesterone is necessary for the development of decidual tissues. In the event of fertilization, high levels of progesterone in the blood are crucial for maintaining pregnancy by promoting uterine growth and inhibiting the effects of factors that cause myometrial contraction. During a cesarean section, the fetus is delivered via a surgical incision made in the woman's abdomen (laparotomy) and in her uterus (hysterotomy). The likelihood of experiencing health issues following a cesarean birth is somewhat increased due to the high number of caesarean sections performed globally in comparison to spontaneous births. Method: 65 pregnant women participated in this cross-sectional study, which ran from October 1, 2022, to March 20, 2023, in the gynecological department of Salah Al Deen General Hospital in the Salah al Deen governorate and in Diyala. Result: As in result of questioners in pregnancies take the progesterone as stabilizer About 75.4% of participants were delivered by cesarean section and only 24.6% were delivered by normal vaginal delivery . Conclusion: The regular use of progestagens for the treatment of impending miscarriage may have contributed to the increased rate of cesarean sections among the participants.

A pivotal role for the IL-1β and the inflammasome in preterm labor

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1β), leading to myometrial contraction. Although IL-1β is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1β was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1β in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1β was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.

User Satisfaction with Application for Postpartum Maternal Gymnastics (SIMPOR)

Introduction: Bleeding is the main cause of 50%-60% morbidity and mortality in the postpartum period due to imperfect myometrial contraction. Postpartum exercise is one of the actions of maximizing uterine contractions. It's accelerate uterine involution. Technology development very fast today, improvement of postpartum android base application that's applicable, educative and informative is needed. This study aims to develop a postpartum maternal exercise application (SIMPOR) for postpartum mothers using Android then test them until obtaining descriptions about satisfaction with the SIMPOR application. Methods: This study used a Research and Development method (R&amp;D) with 152 respondents taken by proportional stratified random sampling. Data analysis was chi-square with univariate and bivariate. Results: The majority of participants were aged in 20-40 years old (98%), educational majority in higher education (59.9%), most of the respondents were housewives (65.8%), having more than one toddler (77.6%), and the average of toddler age was less than 2 years old (84.2%). Most of the respondents' satisfaction with the SIMPOR application was very satisfied (88.16%); 3) There was a relationship between mother's work, parity, and the smallest child age on the satisfaction of using the SIMPOR application with pvalue&lt;0.05. Conclusion: Participants were very satisfied with this SIMPOR application. Based on that result, hopefully postpartum mothers can use this application as postpartum exercise guidance and to monitor their process postpartum period involution.

Changes in the conflicting nongenomic effects of progesterone in rat myometrium during pregnancy

AimsAlthough the functions of progesterone in the myometrium are well-established, the nongenomic effects of progesterone in pregnant myometrial contractions are still unclear. Therefore, this study aimed to investigate changes in the nongenomic effects of progesterone during pregnancy. Main methodsMyometrial strips were obtained from non-pregnant, pregnant, and postpartum rats, and the nongenomic effects of progesterone in the myometrium during pregnancy were examined. Additionally, the influence of actinomycin D and cycloheximide and the effects of Org OD-02-0 (a specific membrane progesterone receptor (mPR) agonist) in the myometrium were investigated. Moreover, DNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to identify genes involved in progesterone-induced effects in the myometrium. Key findingsProgesterone did not cause rhythmic contractions in non-pregnant myometrium but induced rhythmic contractions in pregnant myometrium, with the effects peaking at 20 d + 8 h of pregnancy. However, myometrial contractions decreased after delivery and were restored to non-pregnant levels at 7 d postpartum. Additionally, progesterone stably inhibited high KCl-induced myometrial contractions during pregnancy. Moreover, the nongenomic effects of progesterone were unaffected by actinomycin D or cycloheximide, and Org OD-02-0 effectively mimicked these effects. DNA microarray analysis and qRT-PCR revealed a significant increase in mPRβ gene expression during pregnancy. However, mPRα, mPRγ, mPRδ, and mPRε expression levels remained unchanged. SignificanceThe stimulatory nongenomic effect of progesterone, which was inducible and mPRβ-dependent during pregnancy, may be involved in parturition. The inhibitory effect, which was constitutive and depended on other mPRs, may be involved in pregnancy maintenance.

Dysmenorrhea, a Narrative Review of Therapeutic Options.

Dysmenorrhea is the most common pathology women of childbearing age face. It is defined as painful uterine cramping associated with menstruation. Primary dysmenorrhea occurs in the absence of an organic cause, whereas secondary dysmenorrhea is pelvic pain associated with an underlying pelvic pathology. The purpose of this review is to discuss the pathophysiology of dysmenorrhea and provide a discussion of pharmacologic and non-pharmacologic treatment options. Prostaglandins play a large role in the pathophysiology of dysmenorrhea by causing myometrial contraction and vasoconstriction. The first-line treatment for dysmenorrhea is with nonsteroidal anti-inflammatory drugs due to the inhibition of cyclooxygenase enzymes, thereby blocking prostaglandin formation, as well as hormonal contraception. Other pharmacologic treatment options include Paracetamol, as well as Gonadotrophic Release Hormone Analogs, which are typically used in the treatment for endometriosis. Non-pharmacologic treatments with strong evidence include heat therapy and physical exercise. There are less evidence-based data behind other modalities for treating dysmenorrhea, such as dietary supplements, acupuncture, and transcutaneous nerve stimulation, and these methods should be used in conjunction with first-line therapy after a discussion of risks and benefits. Lastly, for women who fail medical management, surgical options include endometrial ablation, presacral neurectomy, and laparoscopic uterosacral nerve ablation. Further research is needed to measure the socioeconomic burden of dysmenorrhea on the healthcare system and to evaluate the efficacy of treatment combinations, as a multi-modal approach likely provides the most benefit for women who suffer from this condition.

317 A 3D printed device for electrophysiological measurement of myometrial smooth muscle cell contractions in vitro

317 A 3D printed device for electrophysiological measurement of myometrial smooth muscle cell contractions in vitro

The Relationship Between Midwives' Knowledge and Attitudes Toward The Provision of Acupressure to Reduce Pain During Labor

Myometrial contractions, which cause labor pain, are a physiological process that varies in intensity depending on the individual. Most women who go through labor feel pain, but not all of them deal with it well. Anxiety and irregular labor might result from improper management of labor pain. It is possible to lessen labor pain by using both pharmaceutical and non-pharmacological interventions. In order to prepare moms and lower maternal anxiety during labor, non-pharmacological therapies like acupressure are thought to lessen the severity of labor pain. From August to October 2023, research using a cross-sectional study design was carried out at the Independent Midwife Practice in Padang City. Up to 40 midwives who worked or had their own independent midwifery practice in Padang City made up the research sample. Systematic random sampling was used to collect the samples. Chi square analysis test (p≤0.05) was used for both univariate and bivariate data analysis. The findings demonstrated that 47.5% of respondents had strong knowledge, and 72.5% had a positive attitude. The bivariate test results, with p values of 0.018 and 0.044, indicated a link between respondents' knowledge and attitude toward the supply of acupressure. When it comes to the providing of labor acupressure, knowledge and attitude are significantly correlated.

Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.

The uterine contraction during labor, a process with repetitive hypoxia and high energy consumption, is essential for successful delivery. However, the molecular mechanism of myometrial contraction regulation is unknown. Serpin family E member 1 (SERPINE1), one of the most upregulated genes in laboring myometrium in both transcriptome and proteome, was highlighted in our previous study. Here, we confirmed SERPINE1 is upregulated in myometrium during labor. Blockade of SERPINE1 using small interfering RNA (siRNA) or inhibitor (Tiplaxtinin) under hypoxic conditions in myocytes or myometrium invitro showed a decrease contractility, which was achieved by regulating ATP production. Chromatin immunoprecipitation (ChIP-seq), Co-immunoprecipitation (Co-IP), and glutathione-S-transferase (GST) pull down explored that the promoter of SERPINE1 is directly activated by hypoxia-inducible factor-1α (HIF-1α) and SERPINE1 interacts with ATP Synthase Peripheral Stalk Subunit F6 (ATP5PF). Together they enhance hypoxia driven myometrial contraction by maintaining ATP production in the key oxidative phosphorylation pathway. The results provide new insight for uterine contraction regulation, and potential novel therapeutic targets for labor management.

Uterine dynamics, blood profiles, and electronic fetal monitoring of primiparous and multiparous bitches classified according to their weight.

Perinatal mortality occurs in all species. In dogs, mortality rates have been reported to range from 5 to 35%. Electronic fetal and uterine monitoring has recently been used in domestic animals to monitor the mother and newborn before and during parturition. In this way, the fetal heart rate and uterine dynamics can be monitored. This study evaluated the uterine dynamics of bitches with different weights and parity. Ninety-six bitches and their 476 puppies were divided into four experimental groups containing 24 individuals each (12 primiparous bitches and 12 multiparous bitches), according to body weight: G1 (4-8 kg), G2 (8.1-16 kg), G3 (16.1 to 32 kg), and G4 (32.1 to 39.6 kg). The fetal heart rate decelerations (dip 2 patterns), uterine dynamics, and bitches' blood profiles were evaluated, including levels of glucose, lactate, pCO2, pO2, pH, HCO3-, and Ca++. The dam weight can affect the vitality of newborns and the uterine dynamics, with differences in the frequency, intensity, and duration of myometrial contractions. The expulsion interval between puppies was longest in primiparous bitches with low weight and shortest in multiparous bitches with high weight. The expulsion interval and the number of stillborn females were higher in primiparous bitches with high weight. Newborn male puppies were significantly heavier than newborn females.

Upregulated TIMP1 facilitates and coordinates myometrial contraction by decreasing collagens and cell adhesive capacity during human labor.

Myometrial contraction is one of the key events involved in parturition. Increasing evidence suggests the importance of the extracellular matrix (ECM) in this process, in addition to the functional role of myometrial smooth muscle cells, and our previous study identified an upregulated tissue inhibitor of metalloproteinase 1 (TIMP1) in human laboring myometrium compared to nonlabor samples. This study aimed to further explore the potential role of TIMP1 in myometrial contraction. First, we confirmed increased myometrial TIMP1 levels in labor and during labor with cervical dilation using transcriptomic and proteomic analyses, followed by real-time PCR, western blotting, and immunohistochemistry. Then, a cell contraction assay was performed to verify the decreased contractility after TIMP1 knockdown in vitro. To further understand the underlying mechanism, we used RNA-sequencing analysis to reveal the upregulated genes after TIMP1 knockdown; these genes were enriched in collagen fibril organization, cell adhesion, and ECM organization. Subsequently, a human matrix metalloproteinase (MMP) array and collagen staining were performed to determine the TIMPs, MMPs and collagens in laboring and nonlabor myometrium. A real-time cell adhesion assay was used to detect cell adhesive capacity. The results showed upregulated MMP8 and MMP9, downregulated collagens, and attenuated cell adhesive capacity in laboring myometrium, while lower MMP levels and higher collagen levels and cell adhesive capacity were observed in nonlabor. Moreover, TIMP1 knockdown led to restoration of cell adhesive capacity. Together, these results indicate that upregulated TIMP1 during labor facilitates and coordinates myometrial contraction by decreasing collagen and cell adhesive capacity, which may provide effective strategies for the regulation of myometrial contraction.

Progesterone control of myometrial contractility

During pregnancy, the primary function of the uterus is to be quiescent and not contract, which allows the growing fetus to develop and mature. A uterine muscle layer, myometrium, is composed of smooth muscle cells (SMCs). Before the onset of labor contractions, the uterine SMCs experience a complex biochemical and molecular transformation involving the expression of contraction-associated proteins. Labor is initiated when genes in SMCs are activated in response to a combination of hormonal, inflammatory and mechanical signals. In this review, we provide an overview of molecular mechanisms regulating the process of parturition in humans, focusing on the hormonal control of the myometrium, particularly the steroid hormone progesterone. The primary reason for discussing the regulation of myometrial contractility by progesterone is the importance of the clinical problem of preterm birth. It is thought that the hormonal mechanisms regulating premature uterine contractions represent an untimely triggering of the normal events occurring during term parturition. Yet, our knowledge of the complex and redundant hormonal pathways controlling uterine contractile activity leading to delivery of the neonate remains incomplete. Finally, we introduce recent animal studies using a novel class of drugs, Selective Progesterone Receptor Modulators, targeting progesterone signaling to prevent premature myometrial contractions.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4–5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.