Fetal Membranes Research Articles

Peripartal changes of metabolic and hormonal parameters in Romanian spotted cows and their relation with retained fetal membranes

This clinical study investigates various metabolic and physiological parameters in dairy cows during puerperium. Retained fetal membranes (RFM) is a significant postpartum complication that can affect the overall health, fertility and productivity of dairy cattle. The research focuses on changes in total proteins, albumin, glucose, triglycerides, total cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cortisol, insulin, and insulin-like growth factor 1 (IGF-1) levels among cows experiencing normal post-partum period (NP) and those with RFM. A significant increase in protein levels was noted during the post-partum period in the RFM group, indicating physiological impacts of RFM at this stage. Albumin levels showed significant differences, highlighting a significant biological effect of RFM in the post-partum period. Glucose levels varied significantly in the weeks leading to parturition, suggesting altered metabolic states in cows that suffered RFM. Triglyceride and cholesterol levels were significantly higher during the antepartum period in the group that experienced reproductive failure, indicating substantial alterations in lipid metabolism which could herald the apparition of RFM. AST and ALT levels provided insights into cellular stress and liver function, with significant increases noted around parturition which could be attributed to the substantial physiological strain of parturition itself. Cortisol levels were higher in RFM cows 2 weeks before parturition, which could indicate an increasing stress response or a physiological preparation for the upcoming labor, and may be more pronounced in cows predisposed to RFM. Insulin levels decreased significantly before and at parturition in RFM cows, indicating a strong energy deficit. IGF-1 levels decreased significantly in RFM cows after parturition. Significant changes in metabolic parameters, such as glucose, triglycerides, and cholesterol levels, delineate the pronounced metabolic challenges faced by cows with RFM. The study elucidates that while some variations are noted as parturition approaches, the most substantial impacts attributable to RFM on metabolic and physiological parameters occur after parturition. These changes may have implications for the health, recovery, and productivity of cows postpartum, suggesting the need for targeted management strategies to mitigate the effects of RFM.

A recurrent de novo missense mutation in COL1A1 causes osteogenesis imperfecta type II and preterm delivery in Normande cattle

BackgroundNine male and eight female calves born to a Normande artificial insemination bull named “Ly” were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality.ResultsUsing Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes.ConclusionsIn conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes.

Premature rupture of membrane (PROM) refers to the rupture of membranes before the onset of labor which increases the risk of perinatal morbidity and mortality. Recently, circular RNAs (circRNAs) have emerged as promising regulators of diverse diseases. However, the circRNA expression profiles and potential circRNA-miRNA-mRNA regulatory mechanisms in PROM remain enigmatic. In this study, we displayed the expression profiles of circRNAs and mRNAs in plasma and fetal membranes of PROM and normal control (NC) groups based on circRNA microarray, the Gene Expression Omnibus database, and NCBI's Sequence Read Archive. A total of 1,459 differentially expressed circRNAs (DECs) in PROM were identified, with 406 upregulated and 1,053 downregulated. Then, we constructed the circRNA-miRNA-mRNA network in PROM, encompassing 22 circRNA-miRNA pairs and 128 miRNA-mRNA pairs. Based on the analysis of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene set enrichment analysis (GSEA), DECs were implicated in immune-related pathways, with certain alterations persisting even postpartum. Notably, 11 host genes shared by DECs of fetal membrane tissue and prenatal plasma in PROM were significantly implicated in inflammatory processes and extracellular matrix regulation. Our results suggest that structurally stable circRNAs may predispose to PROM by mediating systemic immune imbalances, including peripheral leukocyte disorganization, local immune imbalance at the maternal-fetal interface, and local collagen disruption. This is the first time to decipher a landscape on circRNAs of PROM, reveals the pathogenic cause of PROM from the perspective of circRNA, and opens up a new direction for the diagnosis and treatment of PROM.

Pregnancy state before the onset of labor: a holistic mechanical perspective

Successful pregnancy highly depends on the complex interaction between the uterine body, cervix, and fetal membrane. This interaction is synchronized, usually following a specific sequence in normal vaginal deliveries: (1) cervical ripening, (2) uterine contractions, and (3) rupture of fetal membrane. The complex interaction between the cervix, fetal membrane, and uterine contractions before the onset of labor is investigated using a complete third-trimester gravid model of the uterus, cervix, fetal membrane, and abdomen. Through a series of numerical simulations, we investigate the mechanical impact of (i) initial cervical shape, (ii) cervical stiffness, (iii) cervical contractions, and (iv) intrauterine pressure. The findings of this work reveal several key observations: (i) maximum principal stress values in the cervix decrease in more dilated, shorter, and softer cervices; (ii) reduced cervical stiffness produces increased cervical dilation, larger cervical opening, and decreased cervical length; (iii) the initial cervical shape impacts final cervical dimensions; (iv) cervical contractions increase the maximum principal stress values and change the stress distributions; (v) cervical contractions potentiate cervical shortening and dilation; (vi) larger intrauterine pressure (IUP) causes considerably larger stress values and cervical opening, larger dilation, and smaller cervical length; and (vii) the biaxial strength of the fetal membrane is only surpassed in the cases of the (1) shortest and most dilated initial cervical geometry and (2) larger IUP.

Efficacy and Safety of an Inactivated Phase I Coxiella burnetii Vaccine to Control Q Fever in Ruminants: A Systematic Review

Q fever is a disease caused by Coxiella burnetii that affects many animal species and humans. In ruminants, the disease is responsible for several reproductive disorders (such as abortions, stillbirths, premature births, weak offspring, retained foetal membranes and infertility). An inactivated vaccine based on a phase I antigen of C. burnetii is available for cattle, goats and sheep. This review aims to summarise the scientific literature regarding the efficacy and safety of this vaccine to control the infection in these three domestic ruminant species. Forty-five publications and one experimental veterinary thesis reporting on experimental studies, case reports, mathematical modelling and intervention studies were selected according to the PRISMA guidelines. Although some studies lack control groups or statistical analyses, for all three species, published data show that vaccination often results in a reduction in abortions and an improvement in reproductive performance in comparison with absence of vaccination. There is also evidence, including in infected herds and animals, that vaccination is associated with a reduction in bacterial shedding, both in intensity and duration in comparison with absence of vaccination. For these reasons, in case of human outbreaks, vaccination is one of the pillars of control measures. Vaccination is generally well tolerated, despite the rare occurrence of mild, transient side-effects, such as hyperthermia and reduction in milk yield.

A Dynamic Flow Fetal Membrane Organ-on-a-Chip System for Modeling the Effects of Amniotic Fluid Motion.

Fetal membrane(amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. An amnion membrane (AM) organ-on-chip (OOC) was utilized to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 hours flow culture to mimic fluid motion. Static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control for pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to CK-18 ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a flow culture environment is not necessary to mimic any in utero physiologic cellular conditions of fetal membrane-derived cells.

Major Reproductive Disorders Causing Infertility of Dairy Herds in West Shoa Zone, Ethiopia

Reproduction is a complex process in which individuals produce their offspring to perpetuate life. Breeding efficiency depends on the normal function of the reproductive system. Reproductive disorders are the most common problems affecting the reproductive efficiency and productivity of dairy cows. Although, major reproductive disorders are greatly responsible for high economic losses in dairy herds, there is a scarcity the research done and consistent information on the prevalence and relative importance of these problems causing infertility in dairy herds in the West Shoa Zone. Therefore, the current study was conducted in the West Shoa Zone of Oromia regional state to assess the major reproductive disorders of dairy cows in the areas. These districts, namely Adeaberga, Ambo, and Walmera were purposively selected based on their accessibility and potential for dairy production. A total of 180 dairy producers (60 households from each) were randomly selected for individual interviews using a semi-structured questionnaire. The major reproductive disorders found were 82.2% repeat breeding, 22.2% calf mortality, 27.2% retention of the fetal membrane, 23.3% abortion and 16.3% stillbirth. The prevalence of reproductive problems showed a significant difference within the woredas. The prevalence of repeat breeding, retained fetal membrane and calf mortality were severe in Walmera districts compared to the remaining two districts whereas the prevalence of abortion and stillbirth were severe in Adeaberga. Repeat breeding shows a higher prevalence whereas the stillbirth rates show a lower prevalence. The ultimate goal of dairy herd production is to increase milk yield and manipulate early first service and calving, lower the calving interval and days open and decrease the number of services per conception. However, repeat breeding, retained fetal membrane, abortion, calf mortality and stillbirth were the major causes of infertility in dairy cows in the study areas. Proper breeding strategies and keeping the health conditions of dairy cattle should be employed to ensure improvements in fertility traits.

Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes.

Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy.

The association between the degree of cervical dilatation before ultrasound and physical examination indicated cerclage and subsequent neonatal outcomes.

Preterm identification of cervical dilation in pregnant women leads to the application of emergency cervical cerclage with an expectation of achieving term delivery. However, this is not always feasible. Short- and long-term neonatal complications post-preterm birth pose a significant challenge. It is crucial to anticipate potential complications and understand the possibilities of postpartum development as they can be encountered. We aimed to evaluate the effect of the degree of cervical dilatation before ultrasound and physical examination-indicated cerclage in singleton pregnancies presenting with premature cervical dilatation with bulging fetal membranes (rescue cerclage) on subsequent neonatal outcomes. In this retrospective clinical study, over a 10-year period between January 2009 and January 2019, 72 singleton pregnancies undergoing rescue cerclage were included and divided into two groups according to pre-cerclage cervical dilatation: Group 1 (n = 33) and Group 2 (n= 39) with cervical dilatation ≤3 cm and >3 cm, respectively. Latency period for pregnancy prolongation, gestational age at delivery, birth weight, and neonatal morbidity and mortality were compared across the groups. Logistic regression was used to delineate the independent effect of cervical dilatation at cerclage placement on neonatal mortality. Group 2 had a higher delivery rate at ≤28 weeks' gestation (p = 0.007) and lower birth weight (p = 0.002) compared to Group 1, with an increased mean latency period in Group 2 (90 ± 55 days versus 52 ± 54 days, p = 0.005). The newborn intensive care unit (NICU) requirement, respiratory distress syndrome (RDS), neonatal jaundice and sepsis, and retinopathy of prematurity (ROP) were more frequent in Group 2. Neonatal mortality rate was higher (52.6% versus 24.2%, p = 0.015) and intact survival was lower (23.1% versus 48.4%, p = 0.013) in Group 2, whereas rates of cerebral palsy (8% and 9%, respectively) were similar between the groups (p = 0.64). Advanced cervical dilatation (>3 cm) during physical examination-indicated cerclage in singleton pregnancies is associated with earlier delivery, leading to increased neonatal morbidity and mortality when compared with pregnancies having lesser degrees of cervical dilatation at cerclage. However, short-term poor neurological outcomes seem comparable.

In vitro mRNA-S maternal vaccination induced altered immune regulation at the maternal-fetal interface.

Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology. This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs). We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs). Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1β remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs. In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications.

Delicate threads: A case study on velamentous placenta and its clinical significance

Velamentous placenta insertion is a rare and potentially serious pregnancy complication involving the abnormal attachment of the umbilical cord to the fetal membranes rather than to the placenta.This case report details the management of a 23-year-old primigravida at 38 weeks of gestation who presented to the labor room in spontaneous labor.Initial examination revealed a term-size uterus, vertex presentation, and moderate contractions,with a fetal heart rate of 144/min. Despite an unremarkable start to labor, persistent fetal heart decelerations post-amniotomy led to the discovery of velamentous insertion of the placental cord.This case discusses the challenges, decision-making process, and outcomes associated with this rare condition, ultimately resulting in an uneventful postoperative period and successful discharge on the 5th day for both mother and baby.

Heterogeneity of mesenchymal cells in human amniotic membrane at term.

There is increasing interest in understanding the tissue biology of human amniotic membrane (hAM) given its applications in medicine. One cellular component is mesenchymal cells, which can be extracted, cultured and differentiated "in vitro" into various cell types. These studies show that there is heterogeneity among mesenchymal cells. The aim of this work is to study the membrane in situ to determine whether this cellular heterogeneity exists. The hAMs were obtained from caesarean deliveries at term and analyzed by histological techniques. Types I-III mesenchymal cells and Hofbauer were distinguished by light microscopy. Histochemically, mesenchymal cell types showed successively increasing positivity to: PAS, vimentin, fibronectin, and Concanavalin-A; VGEF, TGF-β2, PDGF-C, FGF-2. By the semiquantitative point of view, the percentage of Type II cells was 60%, significantly higher than the other types. With transmission electron microscopy, an intermediate cell type between II-III was observed. Strong vesiculation of the rough endoplasmic reticulum (RER) with exocytosis was observed. In addition, an accumulation of a similar material to the extracellular matrix in the RER caused its dilation especially in type IIITEM cells. Some of this material acquired a globular structure. These structures were also found free in the extracellular matrix. In conclusion, the mesenchymal cells of the fibroblastic layer of the hAMs studied are heterogeneous, with some undifferentiated and others with a probably senescent fibroblastic phenotype with accumulation in their RER of fibronectin. These results may be of interest to extract mesenchymal cells from hAMs for use in regenerative medicine and to better understand the mechanisms of fetal membrane rupture.

Emerging Risk of Microplastics on Health, Agriculture and Environment

Exposure to microplastics is unavoidable, and a vast amount of microplastics are traveling around the oceans. Microplastics are considered one of the major potential pollutants due to their exposure and interference with the health of humans, animals, aquatic species, agriculture, etc. Shockingly, the microplastic was also detected in the human placenta (fetal and amniochorial membranes), which could cause long-term effects on human health. The disposal of plastic into the oceans is the most happening process across the globe; thereby, microplastic pollution is evident, leading to a huge risk to marine species. Also, the accumulation of microplastics on soil or land leads to an increase in pH value, thereby affecting the surface water and soil-groundwater medium, eventually affecting plant and human health. At the same time, microplastics and their particles are found in milk, meat, and other edible items, which directly affects human health. The appearance of microplastic particles in insects, birds, animals, and even human blood indicates its adverse effect on the environment. This review has discussed the impact of microplastic on the health of humans, aquatic species, and agriculture.

The effect of inflammatory cytokines on occurrence of retained placenta in cattle

Background: In simple terms, retained placenta is a common issue after parturition in cattle that can affect their reproductive ability. In pregnancies with fetal growth restriction (FGR), the placenta has low anti-inflammatory cytokines and high pro-inflammatory cytokines. By looking at variations in cytokine levels in the blood, we can diagnose the condition. The focus of a recent study was to examine the role of some interleukins (Interleukins -10, Interleukins -6, Interleukins -1β), C-reactive protein (CRP) and Tumor Necrosis Factor (TNF)-α, in retained placenta occurrence in cattle.Methods: The study involved 40 cows, aged 3-8 years in the Salah-Din province. Each animal suffered from retained placenta also eleven healthy cows served as the control group in a period of January to August 2022. The blood serum was analyzed using enzyme immunoassay techniques (ELIZA) to measure the levels of IL-10, IL-6, IL-1β, CRP and TNF-α.Results: Serum levels of IL-10, IL-6, IL-1β, CRP and TNF-α showed a significant increase in cows experiencing retained fetal membranes compared to healthy cows (2.31±0.11 vs 1.41 ±0.07) (10.48±0.24 vs 5.40±0.19), (13.6±2.1 vs 4±0.9), (0.9±0.02 vs 0.32±0.04) and (60.1 ± 12.79 vs 29.5 ± 16.58) respectively.Conclusion: from the present study we conclude that IL10, IL6, IL1β and TNFα play an essential component in retained placenta incidence, and the estimation levels of these parameters in serum may be considered good indicator for occurrence in cattle. RT-PCR revealed increased expression of SDHA genes in the maternal compartment of the placenta.Keywords: Retained placenta; Cytokines; C-reactive protein

Coxiella burnetii and Reproductive Disorders in Cattle: A Systematic Review.

Coxiellosis or Q fever is an infectious zoonotic disease caused by the bacterium Coxiella burnetii. A systematic review using bibliographic research was carried out, and the focus was the relationship between C. burnetii infection and reproductive disorders in cattle [abortion/stillbirth/perinatal morality/weak calves (ASPW complex); retained foetal membranes (RFMs); metritis/endometritis; and infertility/sub-fertility]. The bibliographical search yielded 443 results from databases, but only 61 were deemed eligible. For each disorder, summary tables were prepared, and a scientific evidence score was calculated for each study based on four criteria to help assess the level of evidence for the impact of C. burnetii on the reproductive disorders assessed: type of publication (peer-reviewed or other); type of study (case-control/cohort or other); type of C. burnetii test (direct or indirect); and comparative statistical analysis (yes or no). In addition, summary tables also included information on the study population, country, authors and year of publication, key findings and an assessment of the evidence for an association. For the ASPW complex, RFMs, metritis/endometritis and infertility/sub-fertility, 43, 9, 8 and 19 studies provided data, respectively. On a scale of four, nearly 50% of all study citations had evidence scores of three or four. For ASPW, RFMs and infertility/sub-fertility, there is a significant body of evidence to support a deleterious role for Q fever. In contrast, for metritis/endometritis, the evidence is unclear. It is concluded that there is a substantial need for further research, particularly involving larger animal populations in more controlled settings. To provide more consistency, it is recommended that authors follow more precise definitions of reproductive parameters and more robust diagnostic methodologies.

Analysis of perinatal outcomes for emergency cervical cerclage in singleton pregnancies at 24–28 weeks of gestation

BackgroundCervical cerclage is the only effective treatment for cervical insufficiency, effectively preventing late miscarriage and preterm birth. The effectiveness and safety of emergency cervical cerclage (ECC) as an emergency treatment when the cervix is already dilated or when there is protrusion of the fetal membranes into the vagina remain controversial, especially in pregnancies at 24–28 weeks when the fetus is viable. There is still no consensus on whether emergency cervical cerclage should be performed in such cases.PurposeTo investigate the effectiveness and safety of emergency cervical cerclage in singleton pregnant women at 24–28 weeks of gestation.MethodsThis study employed a single-center prospective cohort design, enrolling singleton pregnant women at 24–28 weeks of gestation with ultrasound or physical examination indicating cervical dilation or even membrane protrusion. Emergency cervical cerclage was compared with conservative treatment. The primary endpoints included a comprehensive assessment of perinatal pregnancy loss, significant neonatal morbidity, and adverse neonatal outcomes. Secondary endpoints included prolonged gestational age, preterm birth, neonatal hospitalization rate, premature rupture of membranes, and intrauterine infection/chorioamnionitis.ResultsFrom June 2021 to March 2023, a total of 133 pregnant women participated in this study, with 125 completing the trial, and were allocated to either the Emergency Cervical Cerclage (ECC) group (72 cases) or the conservative treatment group (53 cases) based on informed consent from the pregnant women. The rate of adverse neonatal outcomes was 8.33% in the ECC group and 26.42% in the conservative treatment (CT) group, with a statistically significant difference (P = 0.06). There were no significant differences between the two groups in terms of perinatal pregnancy loss and significant neonatal morbidity. The conservative treatment group had a mean prolonged gestational age of 63.0 (23.0, 79.5) days, while the ECC group had 84.0 (72.5, 89.0) days, with a statistically significant difference between the two groups (P < 0.001). Compared with CT group, the ECC group showed a significantly reduced incidence of preterm birth before 28 weeks, 32 weeks, and 34 weeks, with statistical significance (P = 0.046, 0.007, 0.001), as well as a significantly decreased neonatal hospitalization rate (P = 0.013, 0.031). Additionally, ECC treatment did not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis, with no statistically significant differences (P = 0.406, 0.397).ConclusionIn singleton pregnant women with cervical insufficiency at 24–28 weeks of gestation, emergency cervical cerclage can reduce adverse neonatal pregnancy outcomes, effectively prolong gestational age, decrease preterm births before 28 weeks, 32 weeks, and 34 weeks, lower neonatal hospitalization rates, and does not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis.

TLR8-activating miR-146a-3p is an intermediate signal contributing to fetal membrane inflammation in response to bacterial LPS.

Preterm birth is the largest contributor to neonatal morbidity and is often associated with chorioamnionitis, defined as inflammation/infection of the fetal membranes (FMs). Chorioamnionitis is characterised by neutrophil infiltration of the FMs and is associated with elevated levels of the neutrophil chemoattractant, interleukin (IL)-8 and the proinflammatory cytokine, IL-1β. While FMs can respond to infections through innate immune sensors, such as toll-like receptors (TLRs), the downstream mechanisms by which chorioamnionitis arises are not fully understood. A novel group of non-classical microRNAs (miR-21a, miR-29a, miR-146a-3p, Let-7b) function as endogenous danger signals by activating the ssRNA viral sensors TLR7 and TLR8. In this study, the pro-inflammatory roles of TLR7/TLR8-activating miRs were examined as mediators of FM inflammation in response to bacterial lipopolysaccharide (LPS) using an in vitro human FM explant system, an in vivo mouse model of pregnancy, and human clinical samples. Following LPS exposure, miR-146a-3p was significantly increased in both human FM explants and wild-type mouse FMs. Expression of miR-146a-3p was also significantly elevated in FMs from women with preterm birth and chorioamnionitis. FM IL-8 and inflammasome-mediated IL-1β production in response to LPS was dependent on miR-146a-3p and TLR8 downstream of TLR4 activation. In wild-type mice, LPS exposure increased FM IL-8 and IL-1β production and induced preterm birth. In TLR7-/-/TLR8-/- mice, LPS exposure was able to initiate but not sustain preterm birth, and FM inflammation was reduced. Together, we demonstrate a novel signalling mechanism at the maternal-fetal interface in which TLR8-activating miR-146a-3p acts as an intermediate danger signal to drive FM inflammasome-dependent and -independent mechanisms of inflammation and, thus, may play a role in chorioamnionitis and subsequent preterm birth.

Evaluation of peritoneal l-lactate concentration in horses in the early post-partum period.

Peritoneal fluid lactate concentration is an important diagnostic tool in horses with abdominal pain. Information on peritoneal lactate concentrations is lacking following parturition in the mare. To compare blood and peritoneal lactate concentrations in a population of mares within 36h post-partum, report a normal reference range and identify any impact of retained foetal membranes (RFMs). This is a retrospective study evaluating healthy mares from which blood and peritoneal samples had been obtained within 36h of parturition. Exclusion criteria included signs of abdominal pain within this period. Data was interrogated for normality using a Shapiro-Wilk test. Wilcoxon signed-rank test and Bland-Altman analysis were used to compare blood and peritoneal lactate concentrations. Linear regression was used to compare age and breed data with peritoneal lactate concentrations. Significance was defined as p<0.05. Forty mares met the inclusion criteria. Mean age was 12.6±4.1 years, and most mares were multiparous (65%). Peritoneal lactate ((1.2 (IQR=0.9-1.6)mmol/L) was increased compared to blood lactate concentration (0.7 (IQR=0-1.1)mmol/L; p<0.001). Plasma total protein (TP) concentrations were 68 (IQR=64-74)g/L and peritoneal protein concentrations 8 (IQR=4-9.7)g/L. Six mares developed RFM. The median fold-increase in peritoneal lactate concentration compared to blood lactate concentration was 0.9 (IQR: 0.01-1.7; range: 0-2.5). The reference range for peritoneal fluid lactate concentration was 0-2.5mmol/L. Peritoneal lactate concentrations in healthy post-partum mares remained within the normal reference range and were not influenced by RFM or parturition. Increased peritoneal lactate in this group warrants further investigation.

A New Tool to Assess the Economic Impact of Q Fever on Dairy Cattle Farms.

To support farmers in their decisions related to Q fever, a dedicated economic assessment tool is developed. The present work describes the calculator, its economic rationale, and the supporting assumptions. The calculator integrates a yearly compartmental model to represent population dynamism and the main interactions between disorders linked to Q fever, especially reproductive disorders (abortion, retained foetal membranes, purulent vaginal discharge and endometritis, extra services, and calving-conception delays). The effects of the nontangible cost of the disease on human health, the welfare of the animals, and the workload of farmers were not integrated into the model. The model shows high-level sensitivity to the prevalence of Q fever in the herd prevaccination and to the costs of abortion and extra days of calving-conception intervals. Breakeven points, i.e., cost values that allow us to achieve positive vaccination benefits, are also reported. For herds with moderate or high prevalence rates of Q fever prevaccination (>30%), a vaccination benefit is observed. The vaccine should be considered a type of insurance in herds with low prevalence rates of Q fever prevaccination (≤20%). The calculator was developed to aid decision-making at the farm level, and no conclusion can be extrapolated as a generic trend based on the present work.

CircAMN1-Mediated Ferroptosis Regulates the Expulsion of Placenta in Trophoblast Cells.

After delivery, the death of trophoblast cells can promote the expulsion of the placenta. Ferroptosis, an iron-dependent programmed cell death, is involved in mammalian development. Circular RNAs are associated with placental development; however, it is unclear whether circular RNAs regulate the expulsion of fetal membranes through ferroptosis. The gene expression profiles in the tail vein blood of Holstein cows with normal and retained placentas were investigated using RNA sequencing and a GSE214588 dataset. circAMN1 and SLC39A8 expression was significantly downregulated in the blood of cows with a retained placenta, whereas miR-205_R-1 expression was significantly upregulated. We validated erastin-induced ferroptosis in trophoblast cells. Transfection with si-circAMN1 and miR-205_R-1 mimic reduced intracellular total iron, Fe2+, and glutathione disulfide levels; increased intracellular glutathione levels and glutathione/glutathione disulfide; and enhanced cell viability in these cells. In contrast, transfection with pcDNA3.1 circAMN1 and an miR-205_R-1 inhibitor promoted ferroptosis. As an miR-205_R-1 sponge, circAMN1 regulated the expression of SLC39A8 to control erastin-induced ferroptosis and regulated the proliferation, invasion, and migration of trophoblast cells. Our findings provide a theoretical basis for studying the mechanism by which programmed cell death regulates fetal membrane expulsion and indicate its potential as a therapeutic target for placenta retention.