Chorioamniotic Membranes Research Articles

Quincke versus Diamond-Tip Needles for Entry in Placental Laser Surgery for Twin-to-Twin Transfusion Syndrome.

Chorioamniotic membrane separation (CAS), preterm prelabor rupture of membranes (PPROM), and preterm delivery (PTD) remain as major complications of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS). We sought to examine whether use of Quincke-tip needles for initial entry during FLP reduces the risk of these complications. This is a secondary analysis of prospectively collected data from patients that had FLP for TTTS at a single tertiary care center (2011-2021). We excluded patients for whom direct trocar entry was used. Patients for whom a Quincke-tip needle was used were compared to those for whom a diamond-tip needle was used during Seldinger entry. Demographics, ultrasound findings and operative characteristics were compared between groups. Postoperative outcomes and complications (including CAS, PPROM, and PTD) were also compared. Multivariate logistic regression models were fit to assess independent risk factors for complications. 386 patients met inclusion criteria; Quincke-tip needles were used in 81 (21.0%) cases, while diamond-tip needles were used in 305 (79.0%). Rates of CAS (11.1 vs. 9.5%, p = 0.67) and PPROM (44.4 vs. 41.0%, p = 0.57) were similar between groups. Patients in the Quincke-tip group delivered 1.5 weeks earlier than those in the diamond-tip group (30.5 vs. 32.0 weeks, p = 0.01). However, these patients were more likely to be delivered for maternal (35.9 vs. 19.0%) and fetal (23.1 vs. 15.3%) indications (p < 0.01). In multivariate analysis, needle type was not identified as an independent risk factor for PPROM. However, Quincke-tip needle use was associated with PTD less than 32 weeks (aOR 1.74, 95% CI: 1.02-2.97, p = 0.043). Membrane complications following FLP were not associated with the needle type used for entry. Earlier delivery in the Quincke-tip group was likely attributable to higher rates of delivery for maternal and fetal indications, and not membrane complications. The needle chosen for entry is likely best determined by operator preference.

Molecular investigation of mechanisms considered to cause preterm premature membrane rupture

Purpose: The aim of this study was to investigate the mRNA expression level of p16, CDK4, CDK6, Cyclin D, RB1, and E2F genes in preterm premature rupture of membrane (PPROM) cases and their roles in etiopathogenesis of PPROM. 
 Materials and Methods: Twenty-one pregnancies with PPROM before 34th gestational weeks (study group) were compared with twenty pregnancies with no complication, who gave birth after 37th gestational-week (control group). Both groups chorioamniotic membranes were compared for mRNA expression of p16, cyclin D, CDK4, CDK6, RB1 and E2F genes.
 Results: The mRNA expression levels of p16, cyclin D, CDK4, CDK6, RB1and E2F genes decreased in the PPROM group compared to control group at a statistically significant level.
 Conclusion: Our findings have shown that oxidative stress may not act on the p16 pathway in these cases. In order to understand the molecular mechanism of PPROM, biomarkers of oxidative stress and aging should be evaluated together with other pathways related to aging and oxidative stress in future studies.

Preparation of single-cell suspensions from the human placenta.

Single-cell RNA-sequencing (scRNA-seq) allows the characterization of cellular composition and interactions in complex tissues. An essential prerequisite for scRNA-seq is the preparation of high-quality single-cell suspensions. So far, no protocols have been described for preparing such suspensions from the placenta, an essential organ for fetal development and a site of maternal-fetal immune interaction. Here we describe a protocol for the preparation of high-quality single-cell suspensions from human placental tissues-namely, the basal plate, placental villi and chorioamniotic membranes. The protocol outlines the collection of tissues from the placenta, tailored dissociation procedures for each tissue, and the cryopreservation of single-cell suspensions for multiplex sequencing library preparation. The protocol can be performed by a qualified investigator with basic working knowledge of placental structure. Moreover, the single-cell suspensions generated by using this protocol are compatible with droplet-based scRNA-seq technology, such as the 10x Genomics Chromium system. This protocol reliably produces single-cell suspensions from the placental tissues with high yield and viability for scRNA-seq. This protocol takes ~6 h to complete from tissue collection to cryopreservation of single-cell suspensions, and an additional 2 h for thawing of cryopreserved single cells.

Plastic and Placenta: Identification of Polyethylene Glycol (PEG) Compounds in the Human Placenta by HPLC-MS/MS System.

The placenta is a crucial interface between the fetus and the maternal environment. It allows for nutrient absorption, thermal regulation, waste elimination, and gas exchange through the mother's blood supply. Furthermore, the placenta determines important adjustments and epigenetic modifications that can change the phenotypic expression of the individual even long after birth. Polyethylene glycol (PEG) is a polyether compound derived from petroleum with many applications, from medicine to industrial manufacturing. In this study, for the first time, an integration of ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry (MS) was used to detect suites of PEG compounds in human placenta samples, collected from 12 placentas, originating from physiological pregnancy. In 10 placentas, we identified fragments of PEG in both chorioamniotic membranes and placental cotyledons, for a total of 36 samples.

Pregnancy outcomes following early fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome at 16 weeks’ gestation

Ample evidence supports fetoscopic laser photocoagulation of placental anastomoses as a first-line treatment for twin-to-twin transfusion syndrome, but little is known about the outcomes following procedures conducted in the early second trimester. This study aimed to evaluate perinatal outcomes following early fetoscopic laser placental photocoagulation performed for twin-to-twin transfusion syndrome at 16 weeks' gestation. This retrospective review included monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome necessitating fetoscopic laser photocoagulation at a single tertiary center from 2012 to 2021. The 2 cohorts were defined as cases undergoing laser surgery at 16+0/7 to 16+6/7 weeks' gestation (early laser group) and those undergoing laser surgery ≥17 weeks' gestation (standard laser group), respectively. Primary outcomes included rates of immediate chorioamniotic membrane separation, preterm premature rupture of membranes, and clinical chorioamnionitis. Secondary outcomes included twin survival rates at birth and 30 days of life. Outcomes were compared between cohorts with a P value of <.05 denoting statistical significance. A total of 343 cases were included (35 early laser participants and 308 standard laser participants). The early laser group typically had higher Quintero staging at the time of the procedure. Following intervention, the early laser group had significantly higher rates of chorioamniotic separation than the standard laser group (34.3% vs 1.3% of cases; P<.001) and higher rates of preterm prelabor rupture of membranes (45.7% vs 25.0%; P=.009) and chorioamnionitis (11.4% vs 1.3%; P=.005). Even after adjustment for higher Quintero staging in the early laser group, twin survival was not significantly different between study groups. Early laser surgery for twin-to-twin transfusion syndrome performed at 16 weeks' gestation is associated with significantly higher rates of chorioamniotic separation, preterm rupture of membranes, and chorioamnionitis. However, twin survival does not seem to be negatively impacted following early laser surgery.

Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology, however, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus. To what extent a SARS-CoV-2 infection of the placenta alters the placental antiviral innate immune response is not well understood. A dysregulated innate immune response in the setting of maternal COVID-19 disease may increase risk for inflammatory tissue injury or placental compromise and contribute to deleterious pregnancy outcomes.ObjectiveWe sought to determine the impact of a maternal SARS-CoV-2 infection on placental immune response by evaluating gene expression of a panel of six antiviral innate immune mediators that act as biomarkers of the antiviral and interferon cytokine response. Our hypothesis was that a SARS-CoV-2 infection during pregnancy would result in an upregulated placental antiviral innate immune response.Study DesignWe performed a case control study on placental tissues [chorionic villous (CV) tissues and chorioamniotic membrane (CAM)] collected from pregnant patients with (N=140) and without (N=24) COVID-19 disease. We performed real-time quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Placental histopathology was evaluated. Clinical data was abstracted. Fisher’s exact test, Pearson correlations, and linear regression models were used to examine proportions and continuous data between patients with active (<10 days since diagnosis) versus recovered COVID-19 (>10 days since diagnosis) at time of delivery. Secondary regression models adjusted for labor status as a covariate and evaluated potential correlation between placental innate immune gene expression and other variables.ResultsSARS-CoV-2 vRNA was detected in placental tissues from 5 women with COVID-19 and from no controls (0/24, 0%). Only 1 of 5 cases with detectable SARS-CoV-2 vRNA in placental tissues was confirmed to express SARS-CoV-2 nucleocapsid and spike proteins in syncytiotrophoblast cells. We detected a significantly lower gene expression of five critical innate immune mediators (IFNB, IFIT1, MXA, IL6, IL1B) in CV and CAM from women with active or recovered COVID-19 compared to controls, which remained significant after adjustment for labor status. There were minimal correlations between placental gene expression and other studied variables including: gestational age at diagnosis, time interval from COVID-19 diagnosis and delivery, pre-pregnancy body mass index, COVID-19 disease severity or placental pathology.ConclusionA maternal SARS-CoV-2 infection was associated with an impaired placental innate immune response in chorionic villous tissues and chorioamniotic membranes that was not correlated with gestational age at COVID-19 diagnosis, timer interval from COVID-19 diagnosis to delivery, maternal obesity, disease severity or placental pathology.

Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity

Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM), the neutrophil infiltration into chorioamniotic membranes, is a major cause of PB. However, several cases of PB have also been reported without apparent pathogenic infection or CAM. Such cases are now attributed to “sterile inflammation.” The concept of sterile inflammation has already attracted attention in various diseases, like cardiovascular diseases, diabetes, and autoimmune diseases; recently been discussed for obstetric complications such as miscarriage, PB, gestational hypertension, and gestational diabetes. Sterile inflammation is induced by alarmins, such as high-mobility group box 1 (HMGB1), interleukins (IL-33 and IL-1α), and S100 proteins, that are released by cellular damage without apparent pathogenic infection. These antigens are recognized by pattern-recognition receptors, expressed mainly on antigen-presenting cells of decidua, placenta, amnion, and myometrium, which consequently trigger inflammation. In reproduction, these alarmins are associated with the development of various pregnancy complications, including PB. In this review, we have summarized the development of PB related to acute CAM, chronic CAM, and sterile inflammation as well as proposed a new mechanism for PB that involves innate immunity, acquired immunity, and sterile inflammation.

Delayed Complete Chorioamniotic Membrane Separation in the Third Trimester Following a Motor Vehicle Collision

Complete separation of the amnion and chorion is a rare pregnancy complication. The proposed causes for chorioamniotic separation are failure of fusion,spontaneous separation, and iatrogenically from invasive prenatal pro-cedures. We present the first reported case of delayed complete chorioamniotic separation following a motor vehicle collision. Close fol-low-up with serial fetal ultrasounds resulted in a favorable outcome

Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis-An Update.

Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and β defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units.

Placental transcriptomic signatures of spontaneous preterm birth

Spontaneous preterm birth accounts for most preterm births and leads to significant morbidity in the newborn and childhood period. This subtype of preterm birth represents an increasing proportion of all preterm births when compared with medically indicated preterm birth, yet it is understudied in omics analyses. The placenta is a key regulator of fetal and newborn health, and the placental transcriptome can provide insight into pathologic changes that lead to spontaneous preterm birth. This analysis aimed to identify genes for which placental expression was associated with spontaneous preterm birth (including early preterm and late preterm birth). The ECHO PATHWAYS consortium extracted RNA from placental samples collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood and the Global Alliance to Prevent Prematurity and Stillbirth studies. Placental transcriptomic data were obtained by RNA sequencing. Linear models were fit to estimate differences in placental gene expression between term birth and spontaneous preterm birth (including gestational age subgroups defined by the American College of Obstetricians and Gynecologists). Models were adjusted for numerous confounding variables, including labor status, cohort, and RNA sequencing batch. This analysis excluded patients with induced labor, chorioamnionitis, multifetal gestations, or medical indications for preterm birth. Our combined cohort contained gene expression data for 14,023 genes in 48 preterm and 540 term samples. Genes and pathways were considered statistically significantly different at false discovery rate-adjusted P value of <.05. In total, we identified 1728 genes for which placental expression was associated with spontaneous preterm birth with more differences in expression in early preterm samples than late preterm samples when compared with full-term samples. Of those, 9 genes were significantly decreased in both early and late spontaneous preterm birth, and the strongest associations involved placental expression of IL1B, ALPL, and CRLF1. In early and late preterm samples, we observed decreased expression of genes involved in immune signaling, signal transduction, and endocrine function. This study provides a comprehensive assessment of the differences in the placental transcriptome associated with spontaneous preterm birth with robust adjustment for confounding. Results of this study are in alignment with the known etiology of spontaneous preterm birth, because we identified multiple genes and pathways for which the placental and chorioamniotic membrane expression was previously associated with prematurity, including IL1B. We identified decreased expression in key signaling pathways that are essential for placental growth and function, which may be related to the etiology of spontaneous preterm birth. We identified increased expression of genes within metabolic pathways associated exclusively with early preterm birth. These signaling and metabolic pathways may provide clinically targetable pathways and biomarkers. The findings presented here can be used to understand underlying pathologic changes in premature placentas, which can inform and improve clinical obstetrics practice.

The ChorioAnchor: Design and Testing of a Novel Chorioamniotic Anchoring Device to Enable Percutaneous Fetoscopic Surgery

Introduction: Percutaneous fetoscopic surgery is hampered by an increased risk of preterm prelabor rupture of membranes (PPROM). Recent surgical techniques have shown that suturing the chorioamniotic membranes following laparotomy and uterine exteriorization is associated with a lower risk of PPROM compared to percutaneous in utero surgery. This study presents the ChorioAnchor, a novel resorbable device that percutaneously anchors the chorioamniotic membranes to the uterine wall. Methods: Human factors testing and peel tests were used to simulate the worst-case in-use loading conditions, establishing the device strength requirements. Tensile testing was used to measure the time-zero strength of the device. Porcine cadaver testing was used to examine ultrasound visibility and acute handling characteristics. Short-term host response was examined through an acute 7-day implantation study in a rabbit model. Results: With a time-zero tensile strength of 47 N, the ChorioAnchor exceeded the established 4 N strength requirement. Both the ChorioAnchor and delivery device were seen to be clearly visible under ultrasound imaging. Short-term host response to the device was well within the range expected for this type of device. Conclusion: The ChorioAnchor meets its engineering requirements in the early stages of implantation. Future studies will examine the kinetics of degradation of the device in vitro and in vivo.

Defining a role for Interferon Epsilon in normal and complicated pregnancies

Interferon epsilon (IFNe) is a recently described cytokine that is constitutively expressed in the female reproductive tract. However, the role of this hormonally regulated cytokine during human pregnancy is poorly understood. Moreover, whether IFNe participates in host immune response against bacteria-driven intra-amniotic infection or cervical human papillomavirus infection during pregnancy is unknown. Herein, using a unique set of human samples derived from multiple study cohorts, we aimed to uncover the role of IFNe in normal and complicated pregnancies. We showed that IFNe is expressed in the myometrium, cervix, and chorioamniotic membranes, and may therefore represent a constitutive element of host defense mechanisms in these tissues during pregnancy. The expression of IFNe in the myometrium and cervix appeared greater in late gestation than in mid-pregnancy, but did not seem to be impacted by labor. Notably, concentrations of IFNe in amniotic fluid, but not cervical fluid, were increased in a subset of women undergoing spontaneous preterm labor with intra-amniotic infection, indicating that IFNe could participate in anti-microbial responses in the amniotic cavity. However, stimulation with Ureaplasma parvum and/or lipopolysaccharide did not enhance IFNE expression by amnion epithelial or cervical cells in vitro, implicating alternative sources of this cytokine during intra-amniotic or cervical infection, respectively. Collectively, our results represent the first characterization of IFNe expression by human reproductive and gestational tissues during normal pregnancy and suggest a role for this cytokine in intra-amniotic infection leading to preterm birth.

A collagen plug with shape memory to seal iatrogenic fetal membrane defects after fetoscopic surgery.

Iatrogenic preterm premature rupture of fetal membranes (iPPROM) after fetal surgery remains a strong trigger for premature birth. As fetal membrane defects do not heal spontaneously and amniotic fluid leakage and chorioamniotic membrane separation may occur, we developed a biocompatible, fetoscopically-applicable collagen plug with shape memory to prevent leakage. This plug expands directly upon employment and seals fetal membranes, hence preventing amniotic fluid leakage and potentially iPPROM.Lyophilized type I collagen plugs were given shape memory and crimped to fit through a fetoscopic cannula (Ø 3 mm). Expansion of the plug was examined in phosphate buffered saline (PBS). Its sealing capacity was studied ex vivo using human fetal membranes, and in situ in a porcine bladder model.The crimped plug with shape memory expanded and tripled in diameter within 1 min when placed into PBS, whereas a crimped plug without shape memory did not. In both human fetal membranes and porcine bladder, the plug expanded in the defect, secured itself and sealed the defect without membrane rupture.In conclusion, collagen plugs with shape memory are promising as medical device for rapid sealing of fetoscopic defects in fetal membranes at the endoscopic entry point.

Maternal septicemia caused by Streptococcus mitis: a possible link between intra-amniotic infection and periodontitis. Case report and literature review

BackgroundIntra-amniotic infection has a strong causal association with spontaneous preterm birth and preterm prelabor rupture of membranes (PPROM). The most common route of intra-amniotic infection is the ascending pathway in which microorganisms from the vagina gain access to the amniotic cavity. Distant microorganisms such as those from the oral cavity have been reported in intra-amniotic infection through hematogenous spreading.Case presentationA 31-year-old gravida 1, para 0 Thai woman at 33+6 weeks’ gestation presented with leakage of vaginal fluid and irregular uterine contraction. She developed fever at 4 h after admission and was later diagnosed with acute chorioamnionitis. A Cesarean section was performed to terminate pregnancy. In addition to a blood culture, the cultures of amniotic fluid, vaginal and chorioamniotic membrane swabs were positive for Streptococcus mitis with identical susceptibility profiles. After the delivery and antibiotic prescription, oral examination showed dental caries and chronic periodontitis.ConclusionsThis is the first case report demonstrating maternal septicemia and intra-amniotic infection caused by S. mitis which might be attributed to periodontitis in women presenting with preterm PROM. We highlighted the association of periodontal disease and preterm labor/PROM syndrome. Oral cavity examination should be included in the prenatal care to ensure good dental hygiene.

Histological severity of maternal and fetal inflammation is correlated with the prevalence of maternal clinical signs.

To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran-Armitage trend test. A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%-30% even in the most severe fetal inflammatory responses.

Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection.

An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal–fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 × 105 CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1β secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2–4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8–24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.

A single-cell atlas of the myometrium in human parturition.

Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type–specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.

Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche

Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. In this study, we demonstrate that vaginal Porphyromonas species secrete broad-acting proteases capable of freely diffusing within the cervicovaginal niche. These proteases degrade collagens that are enriched within the cervix (type I) and chorioamniotic membranes (type IV), as well as fibrinogen, which inhibits clot formation. Bioinformatic queries confirmed the absence of gingipain orthologs and identified five serine, cysteine, and metalloprotease candidates in each species. Inhibition assays revealed that each species’ proteolytic activity can be partially attributed to a secreted metalloprotease with broad substrate specificity that is distantly related to the P. gingivalis endopeptidase PepO. This characterization of virulence activities in vaginal Porphyromonas species highlights their potential to alter the homeostasis of reproductive tissues and harm human pregnancy through clotting disruption, fetal membrane weakening, and premature cervical remodeling.

Collagenase Activity of Vaginal Microbes Associated with Preterm Labour

Collagens in the cervix (type I) and chorioamniotic membranes (type I, IV) play important biomechanical roles in maintaining healthy pregnancy and undergo significant modulation during natural labour progression. However, timing is key: inappropriate remodeling of collagens can trigger premature cervical dilation, chorioamniotic membrane rupture and preterm labour. While up to 40% of preterm labour cases arise from microbial infection, the mechanisms underlying this process are not understood. Notably, select members of the vaginal microbiome have been significantly associated with preterm labour including Sneathia, Prevotella and Porphyromonas species.

The efficacy and safety of vitamin C administration to women with history of premature preterm rupture of membrane in prevention of such event in current pregnancy: Randomized controlled clinical trial

When rupture of membrane happens before onset of labor, the condition in obstetric practice is defined as "Prelabor rupture of membranes (PROM)" leading to leakage of amniotic fluid through ruptured chorioamniotic membranes and the conditions happens before 37 weeks of pregnancy the term "preterm PROM (PPROM)" is applied. Lack of vitamin C has been suggested as a predisposing factor and vitamin C supplementation has been suggested as a preventive measure. This study was aimed to determine the efficacy and safety of administration of vitamin C women with history of premature preterm rupture of membrane in prevention of such event in current pregnancy. The present randomized controlled clinical trial was performed in Maternity and Children Teaching Hospital in Al-Diwaniyah province in Iraq. It included 100 women with previous history of premature preborn rupture of membrane who were randomly allocated into two groups. The first group, the study group included 55 women who received vitamin C supplementation orally staring from 14 weeks gestation and the second group, the reference group was the placebo group (n = 45). Data regarding age, previous abortion, body mass index, number of previous pregnancies and previous abortions were obtained and outcome variables included gestational age at which rupture of membrane happened, gestational age at which delivery happened and birth weight were collected. Vitamin C was able to significantly increase the GA at rupture or membrane (p = 0.033), form 29.00 ± 2.92 weeks to 30.11 ± 2.21 weeks. Vitamin C was also able to significantly increase the GA at birth (p = 0.019), form 32.04 ± 2.88 weeks to 33.31 ± 2.43 weeks. In addition, Vitamin C was also able to significantly increase the birth weight (p = 0.019) from 1951.10 ± 869.72 gram to 2409.10 ± 613.44 gram. Vitamin C Administration to women with previous history of Premature Preterm Rupture of Membrane is efficient and safe in prevention of such event in current pregnancy.