NLRP3 inflammasome is involved in uterine activation for labor at term and preterm

The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.

Risk of cesarean delivery in ongoing pregnancies of nulliparous women after 37 weeks of gestation: a prospective cohort study

Objective: To study the risk of CD for each gestational week among ongoing pregnancies of nulliparous women at term. Design: A retrospective, population-based cohort study from January 1, 2016, through December 31, 2017 Setting: a French perinatal network of the Yvelines district, France Population: 11 308 nulliparous women with a singleton fetus in a cephalic presentation and delivered at term (≥37-week +0 day) Methods: for each week of gestation at term, we defined ongoing pregnancies as all pregnancies undelivered at the start of each week. Regression models adjusted by maternal characteristics and hospital status were used to compare the CD risk between ongoing pregnancies and the pregnancies delivered the preceding week. The same methods were applied to subgroups defined by the mode of labor onset. Main outcome measure: The caesarean delivery rate (CD) Results: Ongoing pregnancies > 40 weeks+0 days were associated with a higher risk of CD compared with pregnancies delivered the previous week: 24.3% in ongoing pregnancies ≥ 40 weeks +0 days versus 19.9% in deliveries between 39 weeks +0 days and 39 weeks+6 days (Odd ratio adjusted of 1.28, 95%CI [1.15-1.44]; 30.4% in ongoing pregnancies ≥ 41 weeks +0 days versus 19.6% in deliveries between 40 weeks +0 days and 40 weeks+6 days (OR 1.73, 95%CI [1.51-1.96]). This was also shown for all modes of labor onset and in every maternity unit. Conclusions: CD rates increased starting at 40 weeks +0 days in ongoing pregnancies, regardless of the mode of labor onset.

Edible Medicinal Plants on Facilitating Childbirth: A Systematic Review

Background: Despite advances and the availability of newer drugs to facilitate childbirth, the interest in using natural treatments is on the rise. More than 20 percent of pregnancies require induction of labor, which is associated with side effects and increased risk of cesarean surgery. For this reason, the use of medicinal plants is considered healthier. Objective: The present study is a systematic review of the role of oral herbs in facilitating childbirth. Results: Twenty clinical trials investigated the impact of edible plants on increasing cervical readiness, stimulating labor onset, reducing pain intensity, and shortening the duration of labor. Five studies have revealed the positive impact of saffron. Two studies reported the same effect by chamomile. Three studies showed the positive impact of boiled dill seeds, and two studies showed the impact of date and date syrup. Another study reported the impact of Descurainia Sophia, and six studies also showed the positive effect of castor oil on uterine stimulation, strengthening and relieving labor pains, which eventually lead to facilitating labor. One study also showed no improvement in bishop score after consumption of primrose capsules. Conclusion: The positive effect of edible medicinal plants on facilitating childbirth has been shown in the mentioned studies. However, more studies with a larger sample size are needed, and there is also a need for a more detailed study of the possible mechanisms of plant effects.

Molecular Mechanism and Pathways of Normal Human Parturition in Different Gestational Tissues: A Systematic Review of Transcriptome Studies

Objective: Genome-wide transcriptomic studies on gestational tissues in labor provide molecular insights in mechanism of normal parturition. This systematic review aimed to summarize the important genes in various gestational tissues around labor onset, and to dissect the underlying molecular regulations and pathways that trigger the labor in term pregnancies.Data sources: PubMed and Web of Science were searched from inception to January 2021.Study Eligibility Criteria: Untargeted genome-wide transcriptomic studies comparing the gene expression of various gestational tissues in normal term pregnant women with and without labor were included.Methods: Every differentially expressed gene was retrieved. Consistently expressed genes with same direction in different studies were identified, then gene ontology and KEGG analysis were conducted to understand molecular pathways and functions. Gene-gene association analysis was performed to determine the key regulatory gene(s) in labor onset.Results: A total of 15 studies, including 266 subjects, were included. 136, 26, 15, 7, and 3 genes were significantly changed during labor in the myometrium (seven studies, n = 108), uterine cervix (four studies, n = 64), decidua (two studies, n = 42), amnion (two studies, n = 44) and placenta (two studies, n = 41), respectively. These genes were overrepresented in annotation terms related to inflammatory and immune responses. TNF and NOD-like receptor signaling pathways were overrepresented in all mentioned tissues, except the placenta. IL6 was the only gene included in both pathways, the most common reported gene in all included studies, and also the gene in the central hub of molecular regulatory network.Conclusions: This systematic review identified that genes involved in immunological and inflammatory regulations are expressed in specific gestational tissues in labor. We put forward the hypothesis that IL6 might be the key gene triggering specific mechanism in different gestational tissues, eventually leading to labor onset through inducing uterine contraction, wakening fetal membranes and stimulating cervical ripening.Systematic Review Registration: Identifier [CRD42020187975].

Features of labor course upon with preterm rupture of membranes and "mature" cervix at gestation of 37 weeks or higher

Introduction. Management and the prevalence of labor complications in patients with premature rupture of the membranes (PROM) is a pressing issue. Aim: to assess the features of childbirth course in patients with PROM during a full-term pregnancy and a favourable cervix. Materials and methods. А prospective analysis of labor course and the postpartum period was performed in 189 patients with a singleton pregnancy with occipital presentation, at least 37-week gestation, of low and moderate risk groups, without contraindications for vaginal delivery. PROM as complicated pregnancy was found in 89 subjects (main group), whereas 100 having labor onset with intact fetal membranes were enrolled into comparison group. The features of labor course were analyzed. Results. Primiparous patients dominated in the main group (66.7 %). The latent period between amniotic fluid discharge to labor onset comprised 4.15 ± 3.48 hours and 3.40 ± 2.13 hours in primiparous and multiparous women, respectively, whereas labor activity in 19 % of women did not develop after 6 hour-latent period. The average duration of labor did not depend on the patient parity and was longer in the group with PROM: 8.06 ± 3.51 hours – in primiparous females, 7.21 ± 2.56 hours – in comparison group (T = –1.99; p = 0.04) due to prolonged first stage of labor. In patients with and without PROM, rate of poor uterine contraction strength was 24.7 % and 18.3 % (p = 0.29), cervical dystocia – 2.25 % and 0 % (p = 0.13), use of oxytocin in childbirth – 35.9 % and 18.3 % (p = 0.007), respectively. Caesarean sections in the main group were recorded in 15 cases (16.85 %), fetal vacuum extraction – 6 cases (6.74 %), whereas in the comparison group – per 2 (2,0 %) cases, respectively (χ2 = 16.13; p < 0.001). Conclusion. Patients with PROM and favourable cervix were shown to have duration of labor, occurrence of operative delivery, rupture of the cervix, and use of oxytocin lasting substantially longer compared to those with the rupture of membranes after onset of the labor. PROM with a favourable cervix occurs more often in primiparous females, which is also coupled to peak rate complications. A 6-hour expectant management is considered as insufficient, because an onset of labor activity in 15.7 % of patients developed after latent period lasting more than 6 hours.

Single-cell transcriptomics analysis showing functional heterogeneity in decidual stromal cells during labor

To investigate the heterogeneity of decidual stromal cells (DSCs) and their functional alterations during delivery, we conducted single-cell RNA sequencing analysis to characterize the transcriptomic profiles of DSCs before and after labor onset. According to their transcriptomic profiles, DSCs (6382 cells) were clustered into five subgroups with different functions. Similar to stromal cells, cells in cluster 1 were involved in cell substrate adhesion. On the other hand, cells in clusters 2 and 3 were enriched in signal transduction-related genes. Labor onset led to significant alterations in many pathways, including the activator protein 1 pathway (all clusters), as well as in the response to lipopolysaccharide (clusters 1–3). The downregulated genes were involved in coagulation, ATP synthesis, and oxygen homeostasis, possibly reflecting the oxygen and energy balance during delivery. Our findings highlight that peripartum DSCs are heterogeneous and play multiple roles in labor.

Recurrent cervical hemorrhages and thromboses associated to pulmonary thrombembolism in a hereditary thrombophilia with heterozygous mutants of MTHFR and PAI-1. Case Report and Pathophysiology Hypotheses

A 30 years Caucazian nullipara, 1 blighted ovum, former Yasmin user (1 year), without antiphospholipid antibodies, prophylactic cervical cerclage at 19 weeks pregnancy, is readmitted in emergency at 21 weeks gestation for heavy pelvic pains, and abundant vaginal red blood loss, with cerclage suppression. Under tocolysis and vaginal progesterone, she presents 3 new episodes of intense pains and red, pulsatile blood loss from different cervical areas at 24- 36 hours after admittance, with mechanical hemostasis by nylon sutures at cervico- vaginal junction. The 4th episode is followed by severe anemia (Hb= 6.03mg/dL, Ht= 18.32%), haemodinamic instability, coagulation disorders- hematomas, generalized petaechia, and at 24 hours after last vaginal sutures she claims thoracic pains, dyspneea, cianosis. There are not registered fetal distress, placental abnormalities, cervical shortness below 2.5 cm (when cerclage), and maternal heart abnormalities at repeated ultrasound examinations. No thoracic computer tomography because maternal refuse. After a cardiologist consultation it is appreciated a mild/moderate pulmonary thrombembolism, without deep legs venous thrombosis, and it is started continuous intravenous anticoagulant therapy – heparine 25,000UI/day x 6 days, then fraxiparine in increased dosages continued to term, and 6 weeks postpartum. The laboratory test confirms intravascular disseminated coagulation with secondary fibrinolysis, and positivity for heterozygous mutants of MTHFR (methylene tetrahydrofolate reductase deficiency C677T and A1298C), and PAI (plasminogen activator inhibitor)-1 (4G). Cesarean delivery is performed at 37 weeks for fetal distress at labor onset, with extraction of a girl 3340g, Apgar=7/8, premature senescent placenta, thin umbilical cord. No maternal and neonate postpartum complications.