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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effect of low-intensity focused ultrasound therapy on postpartum uterine involution in puerperal women: A randomized controlled trial.

BACKGROUND: Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. METHODS: A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. RESULTS: Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. CONCLUSIONS: This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

Simulation of Uterus Active Contraction and Fetus Delivery in ls-dyna.

Vaginal childbirth is the final phase of pregnancy when one or more fetuses pass through the birth canal from the uterus, and it is a biomechanical process. The uterine active contraction, causing the pushing force on the fetus, plays a vital role in regulating the fetus delivery process. In this project, the active contraction behaviors of muscle tissue were first modeled and investigated. After that, a finite element method (FEM) model to simulate the uterine cyclic active contraction and delivery of a fetus was developed in ls-dyna. The active contraction was driven through contractile fibers modeled as one-dimensional truss elements, with the Hill material model governing their response. Fibers were assembled in the longitudinal, circumferential, and normal (transverse) directions to correspond to tissue microstructure, and they were divided into seven regions to represent the strong anisotropy of the fiber distribution and activity within the uterus. The passive portion of the uterine tissue was modeled with a Neo Hookean hyperelastic material model. Three active contraction cycles were modeled. The cyclic uterine active contraction behaviors were analyzed. Finally, the fetus delivery through the uterus was simulated. The model of the uterine active contraction presented in this paper modeled the contractile fibers in three-dimensions, considered the anisotropy of the fiber distribution, provided the uterine cyclic active contraction and propagation of the contraction waves, performed a large deformation, and caused the pushing effect on the fetus. This model will be combined with a model of pelvic structures so that a complete system simulating the second stage of the delivery process of a fetus can be established.

Multichannel mapping of in vivo rat uterine myometrium exhibits both high and low frequency electrical activity in non-pregnancy.

The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20-30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency 'slow wave' which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

Myometrium infection decreases TREK1 through NHE1 and increases contraction in pregnant mice.

Intrauterine infection during pregnancy can enhance uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we used Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, whereas NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells and activated the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by downregulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.NEW & NOTEWORTHY Present work found that infection during pregnancy will increase myometrium contraction. Infection downregulated NHE1 and followed TREK1 expression and activation decrease in myometrium, resulting in increased myometrium contraction.

Quantitative ultrasound measurement of uterine contractility in adenomyotic vs. normal uteri: a multicenter prospective study.

OBJECTIVE: To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method. DESIGN: A multicenter prospective observational study took place in three European centers between 2014 and 2023. SETTING: One university teaching hospital, 1 teaching hospital and 1 specialised clinic. PATIENTS: A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included. INTERVENTION: Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm. MAIN OUTCOMES MEASURES: The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle. RESULTS: Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index. CONCLUSION: Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.

Multiphysics and multiscale modeling of uterine contractions: integrating electrical dynamics and soft tissue deformation with fiber orientation.

The development of a comprehensive uterine model that seamlessly integrates the intricate interactions between the electrical and mechanical aspects of uterine activity could potentially facilitate the prediction and management of labor complications. Such a model has the potential to enhance our understanding of the initiation and synchronization mechanisms involved in uterine contractions, providing a more profound comprehension of the factors associated with labor complications, including preterm labor. Consequently, it has the capacity to assist in more effective preparation and intervention strategies for managing such complications. In this study, we present a computational model that effectively integrates the electrical and mechanical components of uterine contractions. By combining a state-of-the-art electrical model with the Hyperelastic Mass-Spring Model (HyperMSM), we adopt a multiphysics and multiscale approach to capture the electrical and mechanical activities within the uterus. The electrical model incorporates the generation and propagation of action potentials, while the HyperMSM simulates the mechanical behavior and deformations of the uterine tissue. Notably, our model takes into account the orientation of muscle fibers, ensuring that the simulated contractions align with their inherent directional characteristics. One noteworthy aspect of our contraction model is its novel approach to scaling the rest state of the mesh elements, as opposed to the conventional method of applying mechanical loads. By doing so, we eliminate artificial strain energy resulting from the resistance of soft tissues' elastic properties during contractions. We validated our proposed model through test simulations, demonstrating its feasibility and its ability to reproduce expected contraction patterns across different mesh resolutions and configurations. Moving forward, future research efforts should prioritize the validation of our model using robust clinical data. Additionally, it is crucial to refine the model by incorporating a more realistic uterus model derived from medical imaging. Furthermore, applying the model to simulate the entire childbirth process holds immense potential for gaining deeper insights into the intricate dynamics of labor.

Multi-channel electrohysterography enabled uterine contraction characterization and its effect in delivery assessment.

Uterine contractions are routinely monitored by tocodynamometer (TOCO) at late stage of pregnancy to predict the onset of labor. However, TOCO reveals no information on the synchrony and coherence of contractions, which are important contributors to a successful delivery. The electrohysterography (EHG) is a recording of the electrical activities that trigger the local muscles to contract. The spatial-temporal information embedded in multiple channel EHG signals make them ideal for characterizing the synchrony and coherence of uterine contraction. To proceed, contractile time-windows are identified from TOCO signals and are then used to segment out the simultaneously recorded EHG signals of different channels. We construct sample entropy SamEn and Concordance Correlation based feature ψ from these EHG segments to quantify the synchrony and coherence of contraction. To test the effectiveness of the proposed method, 122 EHG recordings in the Icelandic EHG database were divided into two groups according to the time difference between the gestational ages at recording and at delivery (TTD). Both SamEn and ψ show clear difference in the two groups (p<10-5) even when measurements were made 120 h before delivery. Receiver operating characteristic curve analysis of these two features gave AUC values of 0.834 and 0.726 for discriminating imminent labor defined with TTD ≤ 24 h. The SamEn was significantly smaller in women (0.1433) of imminent labor group than in women (0.3774) of the pregnancy group. Using an optimal cutoff value of SamEn to identify imminent labor gives sensitivity, specificity, and accuracy as high as 0.909, 0.712 and 0.743, respectively. These results demonstrate superiority in comparing to the existing SOTA methods. This study is the first research work focusing on characterizing the synchrony property of contractions from the electrohysterography signals. Despite the very limited dataset used in the validation process, the promising results open a new direction to the use of electrohysterography in obstetrics.

Detection of postpartum uterine activity with electrohysterography.

OBJECTIVE: Uterine contractions are essential for childbirth, but also for expulsion of the placenta and for limiting postpartum blood loss. Postpartum hemorrhage is associated with almost 25% of the maternal deaths worldwide and the leading cause of maternal death in most low-income countries. Little is known about the physiology of the uterus postpartum, particularly due to the lack of an accurate measurement tool. The primary objective of this pilot study is to explore the potential of using electrohysterography to detect postpartum uterine contractions. If postpartum uterine activity can be objectified, this could contribute to understanding the physiology of the uterus and improve diagnosis and treatment of postpartum hemorrhage. STUDY DESIGN: In this observational study we included women aiming for a vaginal birth in two large maternity clinics in the Netherlands, Amphia Hospital Breda (group A, N2018-0161) and Máxima Medical Center Veldhoven (group B, N17.149). An electrode patch was placed on the maternal abdomen to record real-time electrical uterine activity until one hour postpartum continuously. In group A, the placement of the patch was lower than in group B. For analysis, tracings were divided into five different phases (1: dilatation until start pushing, 2: from start pushing until childbirth, 3: from childbirth until placental expulsion, 4: first hour after placental expulsion and 5: after one hour postpartum). Readability, signal quality and contraction frequency per hour were assessed. Additionally, patient satisfaction was evaluated through a survey. RESULTS: In total 91 pregnant women were included of whom 45 in group A and 46 women in group B. Complete registrations were obtained throughout the five labor phases with very little artefacts or signal loss. The readability of the tracings decreased after childbirth. A significantly better readability was found in tracings where the patch placement was lower on the abdomen for phases 4 and 5. Contraction frequency was highest during phase 2 and decreased towards phase 5. Women rated the satisfaction with electrohysterography as high and mostly did not notice the patch. CONCLUSION: It is possible to detect uterine activity postpartum with electrohysterography. Further investigation is recommended to improve diagnosis and treatment of postpartum hemorrhage.

Golgi Reassembly Stacking Protein 2 Modulates Myometrial Contractility during Labor by Affecting ATP Production.

The mechanism of maintaining myometrial contractions during labor remains unclear. Autophagy has been reported to be activated in laboring myometrium, along with the high expression of Golgi reassembly stacking protein 2 (GORASP2), a protein capable of regulating autophagy activation. This study aimed to investigate the role and mechanism of GORASP2 in uterine contractions during labor. Western blot confirmed the increased expression of GORASP2 in laboring myometrium. Furthermore, the knockdown of GORASP2 in primary human myometrial smooth muscle cells (hMSMCs) using siRNA resulted in reduced cell contractility. This phenomenon was independent of the contraction-associated protein and autophagy. Differential mRNAs were analyzed using RNA sequencing. Subsequently, KEGG pathway analysis identified that GORASP2 knockdown suppressed several energy metabolism pathways. Furthermore, reduced ATP levels and aerobic respiration impairment were observed in measuring the oxygen consumption rate (OCR). These findings suggest that GORASP2 is up-regulated in the myometrium during labor and modulates myometrial contractility mainly by maintaining ATP production.

Monitoring uterine contractions during labor: current challenges and future directions.

Organ-level models are used to describe how cellular and tissue-level contractions coalesce into clinically observable uterine contractions. More importantly, these models provide a framework for evaluating the many different contraction patterns observed in laboring patients, ideally offering insight into the pitfalls of currently available recording modalities and suggesting new directions for improving recording and interpretation of uterine contractions. Early models proposed wave-like propagation of bioelectrical activity as the sole mechanism for recruiting the myometrium to participate in the contraction and increase contraction strength. However, as these models were tested, the results consistently revealed that sequentially propagating waves do not travel long distances and do not encompass the gravid uterus. To resolve this discrepancy, a model using 2 mechanisms, or a "dual model," for organ-level signaling has been proposed. In the dual model, the myometrium is recruited by action potentials that propagate wave-like as far as 10 cm. At longer distances, the myometrium is recruited by a mechanotransduction mechanism that is triggered by rising intrauterine pressure. In this review, we present the influential models of uterine function, highlighting their main features and inconsistencies, and detail the role of intrauterine pressure in signaling and cervical dilation. Clinical correlations demonstrate the application of organ-level models. The potential to improve the recording and clinical interpretation of uterine contractions when evaluating labor is discussed, with emphasis on uterine electromyography. Finally, 7 questions are posed to help guide future investigations on organ-level signaling mechanisms.

Assessment of uterine contractions in labor and delivery.

Normal labor and delivery are dependent on the presence of regular and effective contractions of the uterine myometrium. The mechanisms responsible for the initiation and maintenance of adequate and synchronized uterine activity that are necessary for labor and delivery result from a complex interplay of hormonal, mechanical, and electrical factors that have not yet been fully elucidated. Monitoring uterine activity during term labor and in suspected preterm labor is an important component of obstetrical care because cases of inadequate and excessive uterine activity can be associated with substantial maternal and neonatal morbidity and mortality. Inadequate labor progress is a common challenge encountered in intrapartum care, with labor dystocia being the most common indication for cesarean deliveries performed during labor. Hereafter, an accurate assessment of uterine activity during labor can assist in the management of protracted labor by diagnosing inadequate uterine activity and facilitating the titration of uterotonic medications before a trial of labor is prematurely terminated. Conversely, the ability to diagnose unwanted or excessive uterine activity is also critical in cases of threatened preterm labor, tachysystole, or patients undergoing a trial of labor after cesarean delivery. Knowledge of uterine activity in these cases may guide the use of tocolytic medications or raise suspicion of uterine rupture. Current diagnostic capabilities are less than optimal, hindering the medical management of term and preterm labor. Currently, different methods exist for evaluating uterine activity during labor, including manual palpation, external tocodynamometry, intrauterine pressure monitoring, and electrical uterine myometrial activity tracing. Legacy uterine monitoring techniques have advantages and limitations. External tocodynamometry is the most widespread tool in clinical use owing to its noninvasive nature and its ability to time contractions against the fetal heart rate monitor. However, it does not provide information regarding the strength of uterine contractions and is limited by signal loss with maternal movements. Conversely, the intrauterine pressure catheter quantifies the strength of uterine contractions; however, its use is limited by its invasiveness, risk for complications, and limited additive value in all but few clinical scenarios. New monitoring methods are being used, such as electrical uterine monitoring, which is noninvasive and does not require ruptured membranes. Electrical uterine monitoring has yet to be incorporated into common clinical practice because of lack of access to this technology, its high cost, and the need for appropriate training of clinical staff. Further work needs to be done to increase the accessibility and implementation of this technique by experts, and further research is needed to implement new practical and useful methods. This review describes current clinical tools for uterine activity assessment during labor and discusses their advantages and shortcomings. The review also summarizes current knowledge regarding novel technologies for monitoring uterine contractions that are not yet in widespread use, but are promising and could help improve our understanding of the physiology of labor, delivery, and preterm labor, and ultimately enhance patient care.

Use of External Uterine Electromyography Across Stage I Labor.

INTRODUCTION: Highly sensitive, external uterine electromyography (EMG) measures myometrial electrical activity and is noninvasive compared with the clinical intrauterine pressure catheter. Most experimental studies have measured EMG in 30-minute epochs, limiting the utility of this instrumentation in intrapartum clinical practice. To test proof of concept, surface uterine EMG contraction activity was continuously collected throughout the first stage of labor from healthy women at term gestation with (n = 3) and without (n = 1) epidural or combined spinal-epidural analgesia for a maximal length of 11 hours and 24 minutes. METHODS: EMG activity was recorded concurrently with tocodynamometer (toco) signals, using a pair of electrodes on the left and right sides of the maternal umbilicus with grounds attached to both hips of the reclining woman in labor. The preamplifier cutoff frequency settings were appropriate to monitor smooth muscle contraction in labor, with the analog high-pass filter set at 0.05 Hz and the low-pass filter at 1.50 Hz. Signals were sampled at 100 Hz, transmitted to a computer, and visualized by Chart 4.2 software. EMG data from epochs at baseline, during the pre-epidural fluid bolus and at the 60-minute post-epidural test dose, and at 3, 5, 6, and 8 cm dilatation were analyzed for burst power spectrum peak frequency (Hz), burst power spectrum amplitude (mV2 ), and burst duration (seconds). RESULTS: Uterine EMG contractile bursts were preceded and followed by a stable baseline and coincided with toco contractions. Movement artifacts were negligible, and large movement artifacts were easily distinguishable. The EMG bursts and toco contractions remained clearly identifiable, even when one woman without epidural analgesia stood beside the bed laboring for approximately 10 minutes. Burst spectral components fell within the expected 0.34-to-1.00 Hz range for term labor. DISCUSSION: High-quality data demonstrate that EMG instrumentation effectively and accurately measures uterine contraction parameters across the first stage of term labor.

Noninvasive electromyometrial imaging of human uterine maturation during term labor.

Electromyometrial imaging (EMMI) was recently developed to image the three-dimensional (3D) uterine electrical activation during contractions noninvasively and accurately in sheep. Herein we describe the development and application of a human EMMI system to image and evaluate 3D uterine electrical activation patterns at high spatial and temporal resolution during human term labor. We demonstrate the successful integration of the human EMMI system during subjects' clinical visits to generate noninvasively the uterine surface electrical potential maps, electrograms, and activation sequence through an inverse solution using up to 192 electrodes distributed around the abdomen surface. Quantitative indices, including the uterine activation curve, are developed and defined to characterize uterine surface contraction patterns. We thus show that the human EMMI system can provide detailed 3D images and quantification of uterine contractions as well as novel insights into the role of human uterine maturation during labor progression.

Functional rewiring of G protein-coupled receptor signaling in human labor.

Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk. Super-resolution imaging with computational modeling reveals OT-dependent reorganization of EP2-OTR complexes to favor conformations for Gαi over Gαs activation. A selective EP2 ligand, PGN9856i, activates the relaxatory/Gαs-cAMP pathway but not the pro-labor/inflammatory responses in term-pregnant myometrium, even following OT. Our study reveals a mechanism, and provides a potential therapeutic solution, whereby EP2-OTR functional associations could be exploited to delay preterm labor.

Fully Automatic Classification of Cardiotocographic Signals with 1D-CNN and Bi-directional GRU.

Prenatal fetal monitoring, which can monitor the growth and health of the fetus, is vital for pregnant women before delivery. During pregnancy, it is essential to classify whether the fetus is abnormal, which helps physicians carry out early intervention to avoid fetal heart hypoxia and even death. Fetal heart rate and uterine contraction signals obtained by fetal heart monitoring equipment are essential to estimate fetal health status. In this paper, we pre-process the obtained data set and enhance them using Hermite interpolation on the abnormal classification in the samples. We use the 1D-CNN and GRU hybrid models to extract the abstract features of fetal heart rate and uterine contraction signals. Several evaluation metrics are used for evaluation, and the accuracy is 96 %, while the sensitivity is 95 %, and the specificity is 96 %. The experiments show the effectiveness of the proposed method, which can provide physicians and users with more stable, efficient, and convenient diagnosis and decision support.

RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth.

In brief: Various etiologies can cause uterine myometrium contraction, which leads to preterm birth. This study demonstrates a new functional relationship between the Ras-related C3 botulinum toxin substrate 1 (RAC1) and uterine myometrium contraction in preterm birth. Abstract: Preterm birth (PTB) is a public health issue. The World Health Organization has recommended the use of tocolytic treatment to inhibit preterm labour and improve pregnancy outcomes. Intrauterine inflammation is associated with preterm birth. RAC1 can modulate inflammation in different experimental settings. In the current study, we explored whether RAC1 can modulate spontaneous uterine myometrium contraction in a mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation. Subsequently, we recorded uterine myometrium contraction and examined uterine Rac1 expression in a mouse model of preterm birth and a case in pregnant women by Western blotting analysis. We also measured progesterone levels in the blood serum of mice. Murine myometrium was obtained 12 h post LPS treatment. Human myometrium was obtained at the time of caesarean section. We found that in the LPS-treated group of mice, uterine myometrium contraction was enhanced, protein levels and activation of RAC1 were increased and serum progesterone levels were decreased. The protein levels of RAC1 were also increased in preterm birth and in pregnant women. NSC23766, a RAC1 inhibitor, attenuated uterine myometrium contraction and diminished RAC1 activation and COX-2 expression. Furthermore, silencing of RAC1 suppressed cell contraction and COX-2 expression in vitro. In conclusion, our results suggested that RAC1 may play an important role in modulating uterine myometrium contraction. Consequently, intervening with RAC1 represents a novel strategy for the treatment of preterm birth.

Uterine slow wave: directionality and changes with imminent delivery.

Objective.The slow wave (SW) of the electrohysterogram (EHG) may contain relevant information on the electrophysiological condition of the uterus throughout pregnancy and labor. Our aim was to assess differences in the SW as regards the imminence of labor and the directionality of uterine myoelectrical activity.Approach. The SW of the EHG was extracted from the signals of the Icelandic 16-electrode EHG database in the bandwidth [5, 30] mHz and its power, spectral content, complexity and synchronization between the horizontal (X) and vertical (Y) directions were characterized by the root mean square (RMS), dominant frequency (domF), sample entropy (SampEn) and maximum cross-correlation (CCmax) of the signals, respectively. Significant differences between parameters at time-to-delivery (TTD) ≤7 versus >7 days and between the horizontal versus vertical directions were assessed.Main results.The SW power significantly increased in both directions as labor approached (TTD ≤ 7d versus >7d (mean±SD):RMSx = 0.12 ± 0.10 versus 0.08 ± 0.06 mV;RMSy = 0.12 ± 0.09 versus 0.08 ± 0.05 mV), as well as the dominant frequency in the horizontal direction (domFx= 9.1 ± 1.3 versus 8.5 ± 1.2mHz) and the synchronization between both directions (CCmax= 0.44 ± 0.16 versus 0.36 ± 0.14). Furthermore, its complexity decreased in the vertical direction (SampEny= 6.13·10-2 ± 8.7·10-3versus 6.50·10-2 ± 8.3·10-3), suggesting a higher cell-to-cell electrical coupling. Whereas there were no differences between the SW features in both directions in the general population, statistically significant differences were obtained between them in individuals in many cases.Significance.Our results suggest that the SW of the EHG is related to bioelectrical events in the uterus and could provide objective information to clinicians in challenging obstetric scenarios.