Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decreased, but this decrease was not statistically significant. Additionally, GRP78 levels increased significantly in the PCOS group. In the PCOS group, the mRNA level, immunostaining intensity of GRP78, and ER damage grade increased, but the uterine tissue calcium levels, and the frequency and amplitude of spontaneous uterine contractions decreased. The results indicated that increased ER stress in myometrial smooth muscle cells may play a causative role in the decreased spontaneous uterine contractions in PCOS.

OBJECTIVE: Aim: To clarify the association between different types of uterine contractility dysfunction and the inflammation of the uterus and chorioamniotic membranes.
METHODS: Materials and Methods: The association between the inflammation of the uterine layers, chorioamniotic membranes, umbilical cord, and different types of labor activity abnormalities was examined in 382 patients with singleton pregnancies at 28-42 weeks\' gestation who underwent Caesarean section (CS) for abnormal uterine contractions and other complications. Statistical analyses included the Mann-Whitney U, Chi-squared test, and logistic regression.
RESULTS: Results: In the control group, slight infiltration with polymorphonuclear leukocytes (PMNs) and macrophages of the myometrium and decidua of the lower uterine segment at term pregnancy was found in 59.7% and 73.6% of cases. The main clinical risk factors for placental and decidual membrane inflammation in patients with excessive uterine activity (EUA) were prematurity, multiparity, group B streptococcus (GBS) colonization, and duration of ruptured fetal membranes before the CS. Moderate or marked myometrial inflammation of both uterine segments in the EUA group was diagnosed only in patients with cervical dilation of >6 cm and duration of labor of >8h. In women with hypotonic uterine activity (HUA), decidual and myometrial inflammation was significantly associated with nulliparity and intrapartum factors, such as protracted active first stage of labor, advanced cervical dilation, and number of vaginal examinations. In all cases, inflammation of the myometrium was accompanied by deciduitis.
CONCLUSIONS: Conclusions: Mild inflammation of the decidual membrane and myometrium of the lower segment at term pregnancy is a common physiological phenomenon contributing to labor initiation. Uterine hyperfunction comes as the response of the unaffected myometrium to the release of high concentrations of proinflammatory cytokines produced by the inflamed decidual and chorioamniotic membranes into the bloodstream. Marked myometrial inflammation that occurs in prolonged labor is an additional factor aggravating the hypotonic uterine activity.

Background Labor induction, a common practice to prevent maternal and fetal complications from prolonged labor, involves stimulating contractions before they begin naturally. This can be achieved through medications, mechanical methods, or surgical interventions. Cervical ripening is crucial for successful delivery. When the cervix is not sufficiently ripe, drugs are often used to augment this process chemically. Objective To evaluate the safety and efficacy of mifepristone for cervical ripening and induction of labor. Method A sample size of 200 was used in this single-blind randomized control trial. Primarily, pregnant women with term pregnancies, Bishop scores <6, and cephalic fetal presentation were included in the study. The study population was randomly divided into test and control groups. The test group (n=100) was administered 200 mg of mifepristone orally, while the control group (n=100) received a placebo. The Bishop score was reassessed 24 hours after mifepristone administration. Patients were taken for labor induction if their Bishop score was >6. For individuals with a Bishop score of <6, 1 mg of dinoprostone gel was administered intracervically once every six hours. Safety and efficacy were assessed by analyzing several parameters associated with labor progression, maternal outcomes, and fetal outcomes. Results The mean age of patients in the test group was 26±4.5 years, while in the control group, it was 26±5 years. The induction-to-delivery interval was notably shorter in the test group (18.8±2.3 hours) than in the control group (19.24±1.8 hours, p<0.0001). After the administration of 200 mg mifepristone, the mean Bishop score in the test group was 5.74±0.8, compared to 5.13±0.76 in the control group. The increase in the Bishop score after mifepristone treatment was significantly higher in the test group than in the control group (p-value=0.013). In the study, 73 (73%) patients in the test group had a normal vaginal delivery (NVD), whereas NVD accounted for 64 (64%) patients in the control group. Instrumental deliveries were less frequent in the test group, accounting for 14 (14%) patients, compared to 16 (16%) patients in the control group. The frequency of lower segment cesarean section (LSCS) was also lower in the mifepristone-treated group at 13 (13%) compared to the control group at 20 (20%). Fetal distress in five (38%) patients and non-progression of labor in 11 (55%) patients were the most frequent indications for LSCS in the test and control groups, respectively. There was no significant difference in neonatal outcomes between the test and control groups. Meconium-stained liquor was the most frequent complication in both the test group (10, 10%) and the control group (5, or 5%). Conclusion Administration of mifepristone effectively increased the Bishop scores and reduced the induction-to-delivery interval compared to controls, highlighting its potential as a cervical ripening agent.

OBJECTIVE: This study aimed to clarify the relationship between fluctuations in uterine stiffness during the third stage of labor and blood loss upon placenta delivery using shear wave elastography.
METHODS: This prospective cohort study enrolled consecutive singleton pregnant women above 37 weeks of gestation who delivered infants transvaginally at a single perinatal center. Shear wave velocities (SWV) were continuously measured during the third stage of transvaginal labor using transabdominal ultrasound and these values were compared between groups with large (≥500 g) and small amounts of bleeding during this stage.
RESULTS: In total, 8 cases of large bleeding and 47 cases of small bleeding were compared. The large amount of bleeding group had a significantly lower median of minimum SWV values (0.97 [0.52-1.01] m/s than the small amount of bleeding group (1.25 [1.04-1.48] m/s p = 0.02). However, no significant differences were observed between the two groups in terms of median, mean, and maximum SWV values. The time from delivery of the infant to placental delivery was significantly longer in the large amount of bleeding group (median time: 370.5 s vs. 274 s, p < 0.05).
CONCLUSIONS: Ultrasound quantification of uterine stiffness using shear wave elastography demonstrated that uterine contractions may influence the biological hemostasis of the uterus during the third stage of labor. Baseline uterine stiffness was weak and a longer duration of placental separation might be associated with cases of large amounts of bleeding during this stage.

OBJECTIVE: The aim of this study was to elucidate the cause and results of contractions occurring in term pregnant women receiving intravenous iron therapy.
METHODS: During 2019-2020, 136 pregnant women beyond 35 weeks of gestation, who received intravenous iron treatment due to iron deficiency anemia, were included through retrospective screening. Iron deficiency anemia was defined as having hemoglobin levels <10 g/dL and ferritin levels <15 ng/mL, and the pregnant women underwent nonstress test before and after treatment.
RESULTS: The average treatment week for the pregnant women was 36.82±0.74, and the presence of regular contractions in post-treatment follow-up nonstress tests was 72.1% (n=98). The average week of birth was 38.48±1.60. Pregnant women with contractions who had previous cesarean were found to have a mean delivery week of 36.82±0.67, which was statistically significant earlier than for nulliparous and multiparous women (p<0.001).
CONCLUSIONS: In pregnant women with iron deficiency anemia who were beyond 35 weeks, temporary regular contractions may be observed in the nonstress test following intravenous iron replacement. We think that this effect may lead to early term birth in pregnant women with a history of cesarean section. It needs to be confirmed by further prospective studies and animal studies.

Uterine atony is a major contributor to postpartum hemorrhage. We previously proposed the novel histological concept of postpartum acute myometritis (PAM) to elucidate the pathophysiology of uterine atony. This concept involves the infiltration of macrophages and neutrophils, as well as mast cell and complement activation in the myometrium. However, the pathological mechanism underlying uterine atony in the context of PAM remains unclear. Herein, we focused on uterine contraction-associated proteins (CAPs) including connexin 43 (Cx43), oxytocin receptors (OXR), prostaglandin receptors EP1, EP3, FP, and protease-activated receptor (PAR)-1. This follow-up study aimed to compare CAP expression between PAM and control groups. We selected 38 PAM subjects from the cases enrolled in our amniotic fluid embolism registry between 2011 and 2018. Control tissues from 10 parturients were collected during cesarean section. We stained the myometrial tissues with the following CAP markers, inflammatory cell markers, and other markers: Cx43, OXR, EP1, EP3, FP, PAR-1, C5a receptor, tryptase, neutrophil elastase, CD68, β-actin, and Na+/K+-ATPase. The immunostaining-positive areas of Cx43, OXR, EP1, EP3, and FP standardized by β-actin in the PAM tissue were significantly smaller than in the control group, whereas those of PAR-1 and Na+/K+-ATPase increased significantly in the PAM group. The Cx43- and OXR-positive areas correlated negatively with the immunostaining-positive cell numbers of CD68 and tryptase with halo, respectively. PAM may impair individual and synchronized myocyte contraction, leading to uterine atony refractory to uterotonics. Further cell-based studies are needed to elucidate the molecular mechanism by which inflammatory cells suppress CAP expression.

BACKGROUND: The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual\'s entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities.
OBJECTIVE: Our goal is to create a non-invasive preclinical imaging pipeline that can longitudinally probe murine placental health in vivo. We use advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development.
METHODS: We implement dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and analysis pipeline to quantify uterine contraction and placental perfusion dynamics. We use optic flow and time-frequency analysis to quantify and characterize contraction-related placental motion. Our novel imaging and analysis pipeline uses subcutaneous administration of gadolinium for steepest slope-based perfusion evaluation, enabling non-invasive longitudinal monitoring.
RESULTS: We demonstrate that the placenta exhibits spatially asymmetric contractile motion that develops from E14.5 to E17.5. Additionally, we see that placental perfusion, perfusion delivery rate, and substrate delivery all increase from E14.5 to E17.5, with the High Perfusion Chamber (HPC) leading the placental changes that occur from E14.5 to E17.5.
CONCLUSIONS: We advance the placental perfusion chamber paradigm with a novel, physiologically based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and remodeling throughout gestation.
CONCLUSIONS: Our pipeline enables the non-invasive, longitudinal assessment of multiple placenta functions from a single imaging session. Our pipeline serves as a key toolbox for advancing research in mouse models of placental disease and disorder.

OBJECTIVE: To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model.
METHODS: Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement.
RESULTS: In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05).
CONCLUSIONS: TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.

Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.

Progesterone (P4), acting via its nuclear receptor (PR), is critical for pregnancy maintenance by suppressing proinflammatory and contraction-associated protein (CAP)/contractile genes in the myometrium. P4/PR partially exerts these effects by tethering to NF-κB bound to their promot-ers, thereby decreasing NF-κB transcriptional activity. However, the underlying mechanisms whereby P4/PR interaction blocks proinflammatory and CAP gene expression are not fully understood. Herein, we characterized CCR-NOT transcription complex subunit 1 (CNOT1) as a corepressor that also interacts within the same chromatin complex as PR-B. In mouse myome-trium increased expression of CAP genes Oxtr and Cx43 at term coincided with a marked decline in expression and binding of CNOT1 to NF-κB-response elements within the Oxtr and Cx43 promoters. Increased CAP gene expression was accompanied by a pronounced decrease in enrichment of repressive histone marks and increase in enrichment of active histone marks to this genomic region. These changes in histone modification were associated with changes in expression of corresponding histone modifying enzymes. Myometrial tissues from P4-treated 18.5 dpc pregnant mice manifested increased Cnot1 expression at 18.5 dpc, compared to vehicle-treated controls. P4 treatment of PR-expressing hTERT-HM cells enhanced CNOT1 expression and its recruitment to PR bound NF-κB-response elements within the CX43 and OXTR promoters. Furthermore, knockdown of CNOT1 significantly increased expression of contractile genes. These novel findings suggest that decreased expression and DNA-binding of the P4/PR-regulated transcriptional corepressor CNOT1 near term and associated changes in histone modifications at the OXTR and CX43 promoters contribute to the induction of myometrial contractility leading to parturition.