Fetal Membranes Research Articles

The effect of histological and subclinical chorioamnionitis and funisitis on breathing effort in premature infants at birth: a retrospective cohort study

Antenatal inflammation in the form of chorioamnionitis (fetal membranes; HCA) and funisitis (umbilical vessels; FUN) is a major risk factor for preterm birth. Exposure to HCA + FUN affects infants by releasing mediators that may suppress respiratory drive. While the association between clinical chorioamnionitis (CCA) and (depressed) spontaneous breathing has been described, we have investigated the association between breathing and HCA + FUN. Infants born < 30 weeks’ gestation with available placental pathology assessments were included. Infants were compared at multiple levels: infants with vs without HCA + FUN (comparison 1) and infants with subclinical HCA + FUN vs infants without any chorioamnionitis (comparison 2). The primary outcome was breathing effort, defined as minute volume (MV) of spontaneous breathing in the first 5 min after birth. We also assessed tidal volume (Vt), respiratory rate (RR), heart rate (HR), oxygen saturation (SpO2) and oxygen requirement (FiO2). Regression analyses were performed to control for confounding factors. One hundred eighty-six infants were included (n = 75 infants with HCA + FUN vs. n = 111 infants without HCA + FUN). Comparison 1: Infants with HCA + FUN had lower gestational ages 26+5 (25+0–28+1; median (IQR) and lower birthweights (mean ± SD; 943 ± 264) compared to infants without HCA + FUN (28+4 (27+0–29+1) weeks, p < 0.001 and 1023 ± 270 g, p = 0.049). Comparison 2: Subclinical HCA + FUN was diagnosed in 46/75 HCA + FUN infants. Infants with subclinical HCA + FUN had lower gestational ages (26+6 (25+1–28+3) vs. 28+4 (27+2–29+1) weeks, p < 0.001) without significant differences for birthweights (987 ± 248 vs. 1027 ± 267 g, p = 0.389) compared to infants without any chorioamnionitis (n = 102 infants). After adjustment, HCA + FUN was associated with lower MV (p = 0.025), but subclinical HCA + FUN was not (p = 0.226). HCA + FUN and subclinical HCA + FUN were associated with lower Vt (p = 0.003; p = 0.014), SpO2 at 5 min (p = 0.021; 0.036) and SpO2/FiO2 ratio (p = 0.028; p = 0.040).Conclusion: HCA + FUN and subclinical HCA + FUN are associated with reduced oxygenation and parameters that reflect breathing effort in premature infants at birth.What is Known:• Acute antenatal inflammation, in the form of chorioamnionitis (fetal membranes) and funisitis (umbilical vessels), affects a large proportion of premature infants.• Clinical chorioamnionitis is associated with reduced breathing effort and oxygenation in premature infants at birth.What is New:• Histological and subclinical chorioamnionitis and funisitis are associated with reduced breathing effort parameters and oxygenation in premature infants at birth.

The Interplay between Oxidative Stress and Fatty Acids Profile in Romanian Spotted Cows with Placental Retention

(1) Background: Retained fetal membranes (RFM) in cattle negatively impact reproduction, calving intervals, and health. This study examined OS markers and fatty acid profiles in Romanian Spotted cattle, comparing cows with normal parturition to those with RFM. Over 9 weeks, serum samples were collected from 22 cows (7 with RFM, 15 normal) at intervals before and after parturition. Placental tissues were also analyzed. The aim was to identify OS biomarkers that predict RFMs, track changes over time, and assess their impact on the placental fatty acid profile. (2) Methods: Samples were analyzed for superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and total antioxidant capacity (TAC). Placental fatty acids were profiled using gas chromatography–mass spectrometry. (3) Results: SOD and CAT activities increased in cows with retained fetal membranes (RFM) before parturition (SOD: p &lt; 0.001, RFM 404.601 ± 20.941 vs. NP 339.101 ± 44.911; CAT: p &lt; 0.01, RFM 121.132 ± 14.831 vs. NP 96.070 ± 2.397), indicating OS. However, significant decreases during labor suggested weakened antioxidant defenses. Total antioxidant capacity (TAC) peaked during parturition in RFM cows (p &lt; 0.0001, 38.780 ± 3.727 vs. 11.150 ± 1.555), signaling heightened stress. Additionally, MDA levels increased before parturition (p &lt; 0.001, RFM 8.424 ± 1.894 vs. NP 3.807 ± 0.484), confirming lipid peroxidation. RFM cows also exhibited higher levels of saturated fatty acids and lower monounsaturated fatty acids, pointing to metabolic stress. (4) Conclusions: This study highlights the role of OS and fatty acid imbalances in RFMs, suggesting potential strategies to improve reproductive outcomes by managing OS.

C/EBPδ deficiency delays infection-induced preterm birth.

Parturition is an inflammation process. Exaggerated inflammatory reactions in infection lead to preterm birth. Although nuclear factor kappa B (NF-κB) has been recognized as a classical transcription factor mediating inflammatory reactions, those mediated by NF-κB per se are relatively short-lived. Therefore, there may be other transcription factors involved to sustain NF-κB-initiated inflammatory reactions in gestational tissues in infection-induced preterm birth. Cebpd-deficient mice were generated to investigate the role of CCAAT enhancer-binding protein δ (C/EBPδ) in lipopolysaccharide (LPS)-induced preterm birth, and the contribution of fetal and maternal C/EBPδ was further dissected by transferring Cebpd-/- or WT embryos to Cebpd-/- or WT dams. The effects of C/EBPδ pertinent to parturition were investigated in mouse and human myometrial and amnion cells. The interplay between C/EBPδ and NF-κB was examined in cultured human amnion fibroblasts. The mouse study showed that LPS-induced preterm birth was delayed by Cebpd deficiency in either the fetus or the dam, with further delay being observed in conceptions where both the dam and the fetus were deficient in Cebpd. Mouse and human studies showed that the abundance of C/EBPδ was significantly increased in the myometrium and fetal membranes in infection-induced preterm birth. Furthermore, C/EBPδ participated in LPS-induced upregulation of pro-inflammatory cytokines as well as genes pertinent to myometrial contractility and fetal membrane activation in the myometrium and amnion respectively. A mechanistic study in human amnion fibroblasts showed that C/EBPδ, upon induction by NF-κB, could serve as a supplementary transcription factor to NF-κB to sustain the expression of genes pertinent to parturition. C/EBPδ is a transcription factor to sustain the expression of gene initiated by NF-κB in the myometrium and fetal membranes in infection-induced preterm birth. Targeting C/EBPδ may be of therapeutic value in the treatment of infection-induced preterm birth.

Mechanism of collagen type IV regulation by focal adhesion kinase during retained fetal membranes in dairy cows

Retained fetal membranes (RFM) is an important reproductive disease in dairy cows, caused by maternal and fetal placental tissue adhesion. The main collagen in maternal and fetal placenta tissues is collagen type IV (COL-IV) and its breakdown is the key to placental expulsion. Focal adhesion kinase (FAK) has been shown to regulate the hydrolysis of Col-IV by affecting the activity of MMP-2 and MMP-9 activity, but the regulation of the mechanisms involved in placenta expulsion in dairy cows after postpartum are still unclear. The aim of this study was to investigate the pathogenic mechanism of RFM by studying the relationship between the FAK signaling pathway and COL-IV regulation. Maternal placental tissues were collected from six healthy and six cows with RFM of similar age, parity, body condition and milk yield at 12 h postpartum. In vitro experiments were performed on bovine endometrial epithelial cells from three groups including a FAK inhibitor group, a FAK activator group and a control group without FAK inhibitor and activator. The abundance of molecules involved in the FAK signaling pathway and COL-IV was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The immunohistochemical results showed that the key molecules of FAK signaling pathway FAK, Src, MMP-2 and MMP-9 and Col-IV were expressed in placental tissues. The expression level of FAK, Src, MMP-2, and MMP-9 were significantly down-regulated (P < 0.05) and the abundances of COL-IV were significantly up-regulated (P < 0.05) in maternal placental tissues of RFM cows compared with healthy cows. In the FAK inhibitor treatment group, the relative expression levels of FAK and other related proteins were significantly down-regulated (P < 0.05) and the relative expression levels of COL-IV were significantly up-regulated (P < 0.05) with the results of the FAK activation group the opposite. These results indicated that FAK in maternal endometrial epithelial cells could regulate the hydrolysis process of Col-IV through the expression of key factors of signaling pathways and promote collagen hydrolysis, which in turn facilitated the process of postpartum placenta expulsion in dairy cows.

Glutamine Attenuates Inflammation and Stimulates Amniotic Cell Proliferation in Premature Rupture of Membranes-related in vitro Models.

Premature rupture of membranes (PROM), with a prevalence of 15.3% in China, frequently results in adverse pregnancy outcomes. In this study, we aimed to identify amino acid metabolites that were differentially expressed in PROM versus healthy controls (HC) using targeted metabolomics and further explored their mechanisms of action with in vitro models.Inclusion and exclusion criteria were established to recruit 50 PROM and 50 HC cases for targeted metabolomics analysis. Twenty-three amino acid metabolites were quantified in the secretions of the posterior vaginal fornix of pregnant women between 31 and 36 weeks of gestation. Glutamine (0.0216 vs. 0.037μg/mg, P = 0.003, AUC = 72.1%) was identified as the most differentially expressed amino acid metabolite between PROM and HC groups, and had a negative correlation with the abundance of Gardnerella (r=-0.3868, P = 0.0055), Megasphaera (r=-0.3130, P = 0.0269), and Prevotella (r=-0.2944, P = 0.0380), respectively.In amniotic epithelial cell and macrophage co-culture model, Glutamine reduced inflammatory cytokines and chemokines expression and suppressed macrophage chemotaxis. In LPS stimulated RAW 264.7 inflammation model, Glutamine inhibited the expression of inflammatory proteins iNOS and COX-2, down-regulated mRNA transcription of TNF, IL-6, and IL-1β, and reduced the production of reactive oxygen species through inhibiting NF-κB signaling pathway, and therefore demonstrated its anti-inflammatory effect. Furthermore, Glutamine protected amniotic epithelial cell from autophagy and stimulated its proliferation, therefore may intensify fetal membrane and prevent PROM in vivo.Our results suggested that low Glutamine level in vaginal secretion can be used as an indicator for PROM, and local Glutamine supplementation is a potential intervention and prevention strategy for PROM.

A new ex vivo model system to analyze factors affecting the integrity of fetal membranes in fetoscopic surgery

We developed an ex vivo model system to analyze the influence of relevant environmental and mechanical factors potentially affecting the integrity of fetal membranes during fetoscopic surgery. The set-up exposes amniochorion membranes to insufflation at predefined levels of gas pressure, flow, humidity, and temperature. Change in fetal membranes stiffness is quantified during the phase mimicking surgery through measurement of membranes’ strain in response to cyclic overpressure. The trocar induced perforation creates a mechanical weakness whose stability is assessed by increasing the insufflation pressure until membrane rupture. Damage of the epithelial cells lining the amnion is assessed through live-dead staining. Initial experiments demonstrated the functionality of the new apparatus and the feasibility of the proposed protocols. Fetal membranes exposed to air with low humidity for approximately 1 h demonstrated significant embrittlement, while their mechanical integrity was maintained in case of gas insufflation at high humidity (air as well as CO2). Under dry circumstances, there was a significant rate of epithelial cell death. Separation of amnion and chorion in the region of the trocar site was visible in all experiments. This new model is a versatile platform for analyzing the mechanical, histological, and biological implications of fetoscopic surgery on fetal membranes.

Case study: May human norovirus infection be associated with premature delivery?

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis. The varying severity of chronic infection in patients with underlying immune deficiencies poses additional burdens on public health. However, the potential effects of HuNoV infection during pregnancy, a specific immune perturbed state, have been rarely reported. Recently, four cases of HuNoV-infected patients in the late stages of pregnancy were admitted to the Guangzhou Women and Children's Medical Center, and premature rupture of membranes as primary adverse outcome was observed in these cases. Samples of fetal accessory tissue were collected from two of these cases at delivery to explore the potential pathogenesis. Pathological analysis showed placental malperfusion in both maternal and fetal vascular, while a decrease in vessels was not observed in villi of placenta. There was obvious pathological change in the chorion of fetal membrane, accompanied by a tendency of Th-1 immune bias. Notably, aggregation of M2 macrophages was observed in the chorion of the fetal membrane, potentially recruited for tissue repair. Next-generation sequencing showed minimal changes in immune pathways within placenta tissue. A gene panel associated with immunosuppression was identified in the fetal membrane of HuNoV-infected women compared to those of normal parturient. Taken together, this study provides clues for the association between the HuNoV and premature delivery, which requires the attention of the clinicians.

Clinical and statistical analysis of the course of preterm birth based on the materials of communal enterprise «Regional Perinatal Center of the Rivne Regional Council» in 2013–2023 years

One of the priority tasks of modern medical science and practice is the preservation of reproductive health and the gene pool of the nation. It is especially difficult to perform this task during the russian war in Ukraine, which has been going on for more than ten years. According to sociologists, the outcomes of a low birth rate for the country will be catastrophic precisely because of the war.One of the reasons for the decline in the quality of health in the future is the increase in the specific weight of premature births, the frequency of which, according to the World Health Organization, has increased in Ukraine already after six months of full-scale war.The objective: to conduct an analysis of the course of premature births in the conditions of war based on the materials of the communal enterprise (CE) “Regional Perinatal Center of the Rivne Regional Council” for 2013–2023.Materials and methods. A retrospective clinical and statistical analysis of 2,742 histories of pregnancy and childbirth of women who were in labor between 22/0–36/6 weeks of gestation in obstetric departments of the communal enterprise “Regional Perinatal Center of the Rivne Regional Council” in 2013–2023 was carried out.Results. According to CE “Regional Perinatal Center of the Rivne Regional Council”, a progressive decrease in the total number of births by 41.9% was observed in the Rivne Region from 2013 to 2023. At the same time, in the general population of women giving birth, the specific rate of premature births did not have a tendency to increase.In the structure of preterm births, early and late preterm births prevailed. The specific gravity of very early preterm births, which are the most unfavorable for perinatal outcomes, did not have a sustained upward trend. At the same time, the frequency of too early premature births among residents of districts and territorial communities of the Rivne region has significantly increased (2013 – 19 (79.2%) cases, 2023 – 17 (100.0%) cases; p&lt;0.05).Every second premature birth occurred within the first day of hospitalization of a pregnant woman, while the specific rate of such too early premature births increased by 3.4 times during the analyzed period, which significantly worsens the chances of survival of newborns and is the reason for their high perinatal morbidity.The number of premature births in pregnant women with multiple pregnancies remains stable. Every third preterm birth took place on the background of early premature rupture of the fetal membranes, while a significant increase in the frequency of this complication was found in women who gave birth at 22/0–27/6 weeks of pregnancy.Traditionally, the specific rate (55.7–57.5%) of surgical delivery by caesarean section of pregnant women and mothers with premature births remains high, which contributed to a reliable reduction of the perinatal mortality rate of premature babies by 13.7% due to the reduction of antenatal losses. Indicators of early neonatal death were formed at the expense of newborns from too early and early premature births in the same ratio.Conclusions. According to thedata of CE “Regional Perinatal Center of the Rivne Regional Council”, there was a progressive decrease in the birth rate in the Rivne Region with a simultaneous stabilization of the number of premature births. The widespread use of a holistic approach during the medical care of pregnant women and the introduction of modern methods of care for premature newborns ensured a significant decrease in the rate of perinatal death of premature infants due to the reduction of antenatal losses.

Markers of epithelial-mesenchymal transformation in placentas from very early preterm births

Premature birth complicates one in ten births in the world, two-thirds of which are caused by spontaneous labor and premature rupture of membranes (PROM). The opinion about the inflammatory origin of preterm birth is generally accepted, more and more attention is devoted to the phenomena of epithelial-mesenchymal transformation (EMT).The objective: to study markers of cell proliferation and EMT in samples of placentas from very early preterm, early preterm and term births.Materials and methods. Placenta samples were examined from 101 women who had labour at 22–27 weeks of gestation on the background of PROM (I group), 102 women who had labour at 22–27 weeks on the background of intact fetal membranes (II group), 100 women who had labour at 28-34 weeks on the background of PROM (III group) and 102 women in labour – at 28-34 weeks on the background of intact membranes (IV group). Samples of 60 placentas from timely normal births were included in the control group.The presence of proliferation factor Ki-67 was determined in placenta samples by immunohistochemical method, cytokeratin-18 content was determined in 10 placentas of each group, and vimentin – in 10 amniotic membrane samples. Regarding the proliferation antigen Ki-67, the placentas were divided according to the detection of the sign in the distal, proximal and basal villi. The expression of cytokeratin and vimentin in syncytium and amnion cells was measured in conventional units and compared between groups.The statistical evaluation of the obtained differences was carried out using the Student’s test.Results. Proliferation antigen Ki-67 was detected in 61.9% of all placentas, including term births. In the groups of very early preterm birth (PB), they were detected mainly in villi of distal localization – in 44.6% in the group of PROM and in 51.0% – in the group of labour on the background of intact membranes. In the case of deliveries on the background of intact membranes in extremely premature terms, only 22.5% of the samples had a positive antigen in the basal villi, on the background of PROM in these terms – in 36.7%, in the groups of early PB – in 79.4% and 74.0% respectively.Distal Ki-67 expression in such placentas was a rare finding – 10.0% in the III group, 11.8% – in the IV group, and 8.3% – in placentas from term deliveries.In all gestational periods, the expression of cytokeratin in amniotic membranes in placentas from births on the background of PROM is statistically lower than in placentas from births on the background of intact membranes.In the case of very early PB, the greater expression of vimentin in the distal villi (0.324±0.001 units in the I group and 0.356±0.007 units in the II group) than in the intermediate villi (0.234±0.004 units and 0.248±0.002 units, respectively) and basal ones (0.178±0.002 units and 0.189±0.006 units, respectively). This once again confirms that the inflammatory reaction and the associated EMT at birth before 28 weeks are mainly of fetal origin.In placentas from early PB, the pattern is the opposite – from 0.345±0.007 units and 0.369±0.009 units in III and IV groups, respectively, in basal villi to 0.257±0.004 units and 0.239±0.005 – in intermediate villi and 0.178±0.009 units and 0.165±0.005 units – in the distal ones.Conclusions. 1. The expression of the inflammatory proliferation marker Ki-67 was detected in two thirds of the studied placentas regardless of the term of delivery, but very early PBs are characterized by the predominant localization of the marker in the distal villi, while in early PBs – in the basal and proximal villi. 2. The expression of EMT markers indicates the fetal origin of the inflammatory response in very early PB – less cytokeratin in syncytial cells and more vimentin in distal chorionic villi. In placentas from early PB and term deliveries, a more pronounced expression of vimentin in the basal vessels of the chorion dominates.

Clinical, Morphological and Multiplex Analysis of a Case of COVID-19-Associated Placental and Fetal Organ Damage at 16 Weeks Gestation

Abstract. COVID-19-associated damage to the placenta and fetal organs is possible among infected pregnant women. This phenomenon is associated with the presence of the virus in the placental tissue itself and transplacental transmission of SARS-CoV-2 from mother to fetus and occurs in case of severe course of the disease in the mother. However, reliable and clinically significant morphological changes in COVID-19-associated placental damage are still a subject of controversy and speculation. The aim of this article is to present a clinical case analysis and evaluation of the morphological features and results of multiplex analysis of COVID-19- associated fetal and placental tissue damage. Materials and methods. Placental and fetal tissue samples were examined using routine histological methods and immunohistochemical studies of the expression of antibodies to CD15 (MMA), CD3 (MRQ-39), CD68 (KP-1), CD138 (DB-A38). The spectroscopic study was performed using the InSpectr M spectrometer with an excitation wavelength of 532 nm. Results The study revealed an inflammatory infiltrate in the fetal membranes, in the umbilical vein wall, in the stroma of the villi, basal plate and intervillous space, forming thrombi of the vessels of the villi, chorionic plate, intervillous space, trophoblast necrosis, abundant deposition of perivillous fibrin. Spectroscopically, signs of changes in the quantitative and qualitative composition of the amino acids proline, phenylalanine, tyrosine and tryptophan, as well as the appearance of non-standard amino acids (hydroxyproline) and protein isoforms, signs of instability of the acid-base balance were revealed. Conclusion. Among the identified changes, both those characteristic of COVID-19-associated placental damage and non-specific ones associated with the body's inflammatory/cytokine response to COVID-19 and persistent placental infection are determined. The results of the multiplex analysis identified a promising direction in understanding the biological basis and essence of this pathology.

Differential use of various types of pessaries in isthmic-cervical insufficiency for prevention of preterm birth: A randomized prospective trial

Background. Obstetric pessary comprises one of the methods for treatment of isthmic-cervical insufficiency. Despite the variety of pessaries produced, the common purpose of their use consists in preventing premature birth. Various types of pessaries correct different cervical parameters, which is not always taken into account by doctors when choosing a pessary and reduces their potential effectiveness. Objective. To substantiate a differentiated approach to the selection of pessary type for correcting isthmic-cervical insufficiency and preventing preterm birth based on the evaluation of cervical parameters. Methods. A randomized prospective study enrolled 90 pregnant women diagnosed with isthmic-cervical insufficiency (ICD-10 code — О.34.3) at 19–24 weeks of gestation. Of these, 41 women underwent correction of isthmic-cervical insufficiency with an obstetric unloading pessary and 49 women — with a perforated cervical pessary. Transvaginal ultrasound cervicometry evaluated the parameters of the cervix before correcting isthmic-cervical insufficiency and in dynamics (once every 4 weeks) after inserting various types of pessaries. Statistical data processing was carried out using Statistica 10.0 (StatSoft, Tulsa, USA) and MedCalc 10.2.0.0 (MedCalc, Mariakerke, Belgium). The differences were considered to be statistically significant at p &lt;0.05. Results. Inserting an obstetric unloading pessary in isthmic-cervical insufficiency decreased the uterocervical angle from 115 (110; 130)° to 100 (90; 115)° (p = 0.021). A decrease in the uterocervical angle was observed during 16-week-use of obstetric unloading pessary. After insertion of perforated cervical pessaries, the length of the closed part of the cervical region increased from 23 (21; 24) mm to 25 (21; 27) mm (p = 0.009) for a period of 4 weeks with a subsequent decrease in this parameter. The effectiveness of both types of pessaries in preventing preterm birth was found to be identical. Urgent delivery occurred in 61% of cases of using an obstetric unloading pessary and in 64.7% of cases of using a perforated cervical pessary (p = 0.993). The gestational age at preterm birth against the background of the use of obstetric unloading pessaries and perforated cervical pessaries was found comparable and amounted to 247 (230; 253) days and 245 (225; 254) days, respectively (p = 0.870). Conclusion. A differentiated approach to selecting a type of pessary for the prevention of premature birth in isthmic-cervical insufficiency is determined by the initial ultrasound parameters of the cervix. Thus, an increase in the uterocervical angle serves as an indication for an obstetric unloading pessary, while a shortened part of the cervical region without an increase in the utero-cervical angle determines the use of a perforated cervical pessary. Additional dynamic ultrasound control after inserting pessaries of any type allows such complications as pessary displacement, cervical edema, amniotic fluid sludge, prolapse of fetal membranes in the vagina, and increased myometrial tone to be timely diagnosed and corrected, thereby increasing the effectiveness of using pessaries.

Rupture of fetal membrane in ectopic tubal pregnancy: A case report and literature review.

Ruptured tubal pregnancies occurring in the second trimester are rare; yet, they pose a critical risk of life-threatening hemorrhage. This study aims to highlight the importance of timely surgical intervention in such cases to prevent fatal outcomes. The case underscores the diagnostic and therapeutic challenges that arise when distinguishing between tubal and abdominal pregnancies, particularly in the presence of hemoperitoneum, which can obscure imaging results. We present a case involving the spontaneous rupture of a tubal pregnancy at 15 weeks and 3 days of gestation. The patient exhibited elevated beta-human chorionic gonadotropin levels. Initial transabdominal ultrasound suggested an abdominal pregnancy, and computed tomography scans supported these findings. Urgent midline laparotomy revealed the condition to be a tubal pregnancy, contrary to initial imaging. The surgical procedure included the removal of the gestational sac and the affected fallopian tube, followed by abdominal closure. Hemoperitoneum was noted to compromise the accuracy of imaging modalities, complicating the preoperative diagnosis. Histopathological examination confirmed the diagnosis of tubal pregnancy. The patient had an uneventful recovery and was discharged 7 days post-surgery with stable hemoglobin levels. This case underscores the importance of considering the differential diagnosis of abdominal versus tubal pregnancy in the presence of hemoperitoneum, due to their differing clinical management needs. It offers insights that may guide clinicians in the timely diagnosis and treatment of advanced tubal pregnancies, where prompt surgical intervention is critical.

METHODS OF TREATMENT OF RETAINED PLACENTA IN FRIESIAN COWS

Retained placenta in dairy cows is when the fetal membrane or placenta does not exit the uterus within 9-12 hours after calving. Retained placenta is a pathological disorder when the placenta does not fall out within a certain period of time after calving. The placenta in cows is most often expelled 6 (77.3%) to 8 hours after calving (Van Werven et al., 1992). The incidence of placental abruption in cows averages 8.6%. The cause of placental exit is not fully understood. There are several factors on which the separation of the fetal placenta from the uterus depends, they can be: genetic (inherited), nutritional, immunological, and as a result of some diseases of the reproductive tract. The causes of placental retention can be: fatigue of the uterus, inflammatory conditions of the bed, an insufficient amount of some hormones, lack of vitamins and/or minerals, toxic effects of some substances and poisons, and mechanical obstacles. The conclusion is that cows with retained placenta belong to the risk group because they are prone to inflammation of the uterus, so they have a prolonged service period and delayed or absent recovery of the cyclic activity of the ovaries, which can be the cause of sterility, temporary or permanent. Treatment of retained placenta should be carried out in time, removing the fetal placenta manually and inserting foaming tablets for intrauterine use. After that, PgF2α and oxytocin are applied.

Hsa-miR-3928–3p targets the CCL3/CCR5 axis to induce amniotic epithelial cell senescence involved in labor initiation

IntroductionSenescence in human amniotic epithelial cells (hAECs) and increased sterile inflammation in the amniotic cavity can lead to the initiation of term labor (TL). We investigated the possible roles of hsa-miR-3928–3p and chemokine ligand 3 (CCL3) in labor initiation and the underlying molecular mechanisms. MethodsMicroarray chip screening was used to analyse the differential expression of miRNAs in amniotic fluid exosomes from women in TL and term not-in-labor. The GEO and miRWalk databases were used to identify differential genes, and a dual luciferase assay was used to verify the relationship. Reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence were used to determine the expression and localization of CCL3/CCR5 in fetal membranes. RT-qPCR and western blotting were used to detect the expression of CCL3/CCR5 in hAECs with hsa-miR-3928–3p knockdown/overexpression. Cell counting kit 8, flow cytometry, EdU proliferation, senescence-associated β-galactosidase, and enzyme-linked immunosorbent assays were performed to detect the impact of hsa-miR-3928–3p on hAEC function. Resultshsa-miR-3928–3p expression was downregulated in TL. CCL3 (macrophage inflammatory protein-1α) was identified as a differentially expressed target gene. hsa-miR-3928–3p targeted the 3′ UTR of CCL3. Downregulation of hsa-miR-3928–3p expression increased CCL3 expression. CCL3, via its CCR5 receptor, decreased the proliferation, but increased the senescence, apoptosis rate, secretion of inflammatory factors (IL-8, TNF-α, and IL-6), and expression of senescence-associated protein p21 in hAECs. Discussionhsa-miR-3928–3p negatively regulates CCL3, promoting hAEC senescence through the CCL3-CCR5 axis and inducing signals for labor initiation. These findings provide novel insights for labor initiation in clinical settings.

Intrauterine Shaping of Fetal Microbiota.

Mechanisms resulting from the physiological immaturity of the digestive system in children delivered before 32 weeks of gestation and, in particular, different interactions between the microbiome and the body have not been fully elucidated yet. Next-generation sequencing methods demonstrated the presence of bacterial DNA in the placenta and amniotic fluid, which may reflect bacterial populations that initiate intestinal colonization in utero. Numerous studies confirmed the hypothesis stating that intestinal bacteria played an important role in the pathogenesis of necrotizing enterocolitis (NEC) early- and late-onset neonatal sepsis (EONS and LONS). The model and scale of disorders within the intestinal microbiome are the subject of active research in premature infants. Neonatal meconium was primarily used as an indicator defining the environment in utero, as it is formed before birth. Metagenomic results and previous data from microbiological bacterial cultures showed a correlation between the time from birth to sample collection and the detection of bacteria in the neonatal meconium. Therefore, it may be determined that the colonization of the newborn's intestines is influenced by numerous factors, which may be divided into prenatal, perinatal, and postnatal, with particular emphasis put on the mode of delivery and contact with the parent immediately after birth. Background: The aim of this review was to collect available data on the intrauterine shaping of the fetal microbiota. Methods: On 13 March 2024, the available literature in the PubMed National Library of Medicine search engine was reviewed using the following selected keywords: "placental microbiome", "intestinal bacteria in newborns and premature infants", and "intrauterine microbiota". Results: After reviewing the available articles and abstracts and an in-depth analysis of their content, over 100 articles were selected for detailed elaboration. We focused on the origin of microorganisms shaping the microbiota of newborns. We also described the types of bacteria that made up the intrauterine microbiota and the intestinal microbiota of newborns. Conclusions: The data presented in the review on the microbiome of both term newborns and those with a body weight below 1200 g indicate a possible intrauterine colonization of the fetus depending on the duration of pregnancy. The colonization occurs both via the vaginal and intestinal route (hematogenous route). However, there are differences in the demonstrated representatives of various types of bacteria, phyla Firmicutes and Actinobacteria in particular, taking account of the distribution in their abundance in the individual groups of pregnancy duration. Simultaneously, the distribution of the phyla Actinobacteria and Proteobacteria is consistent. Considering the duration of pregnancy, it may also be concluded that the bacterial flora of vaginal origin dominates in preterm newborns, while the flora of intestinal origin dominates in term newborns. This might explain the role of bacterial and infectious factors in inducing premature birth with the rupture of fetal membranes.

Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes

BackgroundPremature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing.MethodsAn in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing.ResultsGalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05).ConclusionsGalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

The dual role of glucocorticoid regeneration in inflammation at parturition.

Fetal membrane inflammation is an integral event of parturition. However, excessive pro-inflammatory cytokines can impose threats to the fetus. Coincidentally, the fetal membranes express abundant 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which generates biologically active cortisol to promote labor through induction of prostaglandin synthesis. Given the well-recognized anti-inflammatory actions of glucocorticoids, we hypothesized that cortisol regenerated in the fetal membranes might be engaged in restraining fetus-hazardous pro-inflammatory cytokine production for the safety of the fetus, while reserving pro-labor effect on prostaglandin synthesis to ensure safe delivery of the fetus. The hypothesis was examined in human amnion tissue and cultured primary human amnion fibroblasts as well as a mouse model. 11β-HSD1 was significantly increased in the human amnion in infection-induced preterm birth. Studies in human amnion fibroblasts showed that lipopolysaccharide (LPS) induced 11β-HSD1 expression synergistically with cortisol. Cortisol completely blocked NF-κB-mediated pro-inflammatory cytokine expression by LPS, but STAT3-mediated cyclooxygenase 2 expression, a crucial prostaglandin synthetic enzyme, remained. Further studies in pregnant mice showed that corticosterone did not delay LPS-induced preterm birth, but alleviated LPS-induced fetal organ damages, along with increased 11β-HSD1, cyclooxygenase 2, and decreased pro-inflammatory cytokine in the fetal membranes. There is a feed-forward cortisol regeneration in the fetal membranes in infection, and cortisol regenerated restrains pro-inflammatory cytokine expression, while reserves pro-labor effect on prostaglandin synthesis. This dual role of cortisol regeneration can prevent excessive pro-inflammatory cytokine production, while ensure in-time delivery for the safety of the fetus.

Anchoring device to prevent membrane detachment and preterm prelabor rupture of membranes after fetal intervention.

To assess the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy. We tested the WestStitch™ suturing device both ex vivo and in vivo. In the ex-vivo studies, 12-Fr trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For the in-vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at approximately 79-90 days' gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane-anchoring integrity when the defect was created and at delivery. Fetal membranes were anchored successfully to the uterine myometrium using the suture-delivery device in all five experiments performed ex vivo. The in-vivo experiments also revealed successful membrane anchoring compared with controls, both at the time of device deployment and 1-9 weeks after the procedure. We successfully anchored amniotic membranes to the underlying myometrium using a suturing device, both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Possible implications of fetal membranes on the impact of subclinical lipopolysaccharide infections in an early gestation rat model.

Possible implications of fetal membranes on the impact of subclinical lipopolysaccharide infections in an early gestation rat model.

Rapid inflammatory responses and subsequent migration of macrophages to fetal membranes in the mouse model of intrauterine infection

Rapid inflammatory responses and subsequent migration of macrophages to fetal membranes in the mouse model of intrauterine infection