Fetal Cord Research Articles

Novel Reassortants of Oropouche Virus (OROV) Are Causing Maternal–Fetal Infection During Pregnancy, Stillbirth, Congenital Microcephaly and Malformation Syndromes

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever.

Is there an association between the serum zonulin concentration and the occurrence of PPROM?

Aims: The aim is to evaluate the association between intestinal permeability, as assessed by zonulin levels, and preterm premature rupture of membranes (PPROM). Methods: A prospective case-control study was conducted involving 44 pregnant women: 22 with PPROM and 22 matched controls. High-risk pregnancies (gestational diabetes, preeclampsia, multiple pregnancies), chronic diseases, and smoking were exclusion criteria. Demographic and clinical data were collected from medical records. Venous and umbilical cord blood samples were obtained post-delivery, centrifuged at 3000 rpm for 10 min, and stored at -80°C. Results: No significant differences were found between the PPROM and control groups regarding age, body-mass index, gravidity, previous abortions, history of preterm rupture of membrane (PROM), or PPROM. Maternal and cord blood zonulin levels were comparable between groups (p>0.05). In the PPROM group, maternal and fetal cord zonulin levels correlated positively with newborn birthweight (r=0.607, p=0.003; r=0.617, p=0.002, respectively). A strong positive correlation was observed between maternal serum and fetal cord blood zonulin levels (r=0.837, p

Effect of abnormal placental cord insertion on hemodynamic change of umbilical cord in a tertiary center: a prospective cohort study.

Our study aims to evaluate the umbilical vein (UV) hemodynamic change in the prenatal cohort of pregnancies diagnosed with abnormal placental cord insertion (aPCI). From January 2022 to December 2022, the fetal umbilical cord insertion site was sonographically examined in singleton fetuses, and umbilical cord blood flow was calculated. The umbilical artery and UV Doppler flow indexes were assessed in cases of normal and abnormal cord insertion. Among 570 singleton fetuses between 18 + 0 and 40 + 6weeks of gestation in the final study, the umbilical vein blood flow (UVBF) in the 3 groups of normal umbilical cord insertions, marginal umbilical cord insertions, and velamentous umbilical cord insertions was 145.39ml/min, 146.18ml/min, and 93.96ml/min, respectively. UVBF was significantly lower in the velamentous cord insertion (VCI) group than in the other groups (P < 0.05). Compared with the normal cord insertions group, lower birth weight (2820 ± 527g vs. 3144 ± 577g, P < 0.05), delivery at an earlier gestational age (38.0 ± 1.55weeks vs. 38.8 ± 2.34weeks, P < 0.05), higher bicarbonate (25.08 ± 1.72mmol/L vs. 22.66 ± 4.05mmol/L, P < 0.05), and higher standard base excess (-1.14 ± 1.50mmol/L vs. -3.30 ± 3.22mmol/L, P < 0.05) were found in the VCI group. We observed lower UVBF volume with aPCI. Hence, we propose UVBF analysis to evaluate fetal aPCI according to UV hemodynamics as an advisory in prenatal care. This would be useful and improve obstetricians' clinical explanation about the potential prenatal consequences so that parents can opt for future prenatal care during pregnancy.

Stem Cell Therapy for the Treatment of Amyotrophic Lateral Sclerosis: Comparison of the Efficacy of Mesenchymal Stem Cells, Neural Stem Cells, and Induced Pluripotent Stem Cells

Background/Objectives: Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is a debilitating, incurable neurodegenerative disorder characterised by motor neuron death in the spinal cord, brainstem, and motor cortex. With an incidence rate of about 4.42 cases per 100,000 people annually, ALS severely impacts motor function and quality of life, causing progressive muscle atrophy, spasticity, paralysis, and eventually death. The cause of ALS is largely unknown, with 90% of cases being sporadic and 10% familial. Current research targets molecular mechanisms of inflammation, excitotoxicity, aggregation-prone proteins, and proteinopathy. Methods: This review evaluates the efficacy of three stem cell types in ALS treatment: mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). Results: MSCs, derived from various tissues, show neuroprotective and regenerative qualities, with clinical trials suggesting potential benefits but limited by small sample sizes and non-randomised designs. NSCs, isolated from the fetal spinal cord or brain, demonstrate promise in animal models but face functional integration and ethical challenges. iPSCs, created by reprogramming patient-specific somatic cells, offer a novel approach by potentially replacing or supporting neurons. iPSC therapy addresses ethical issues related to embryonic stem cells but encounters challenges regarding genotoxicity and epigenetic irregularities, somatic cell sources, privacy concerns, the need for extensive clinical trials, and high reprogramming costs. Conclusions: This research is significant for advancing ALS treatment beyond symptomatic relief and modest survival extensions to actively modifying disease progression and improving patient outcomes. Successful stem cell therapies could lead to new ALS treatments, slowing motor function loss and reducing symptom severity.

Sphingolipids modulate redox signalling during human sperm capacitation.

What role do sphingolipids have in mediating human sperm capacitation? Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion. Bioactive sphingolipids, such as S1P, are fundamental for regulating numerous physiological domains and processes, such as cell membranes and signalling, cell death and proliferation, cell migration and invasiveness, inflammation, and central nervous system development. Semen samples were obtained from a cohort of 10 healthy non-smoking volunteers (18-30 years old) to investigate the role of S1P in sperm. Percoll-selected human spermatozoa were incubated at 37°C for 3.5 h in BWW media with or without foetal cord serum ultrafiltrate (FCSu), sphingosine (Sph), or ceramide (Cer). Spermatozoa were also incubated with or without pharmacological inhibitors of sphingolipid metabolism. Protein tyrosine phosphorylation was determined by immunoblotting. The acrosome reaction was determined by PSA-FTIC labelling of the acrosome and analysed using fluorescence microscopy. Intracellular nitric oxide (NO•) production was determined using a DAF-2DA probe. Immunocytochemistry was performed to localize and assess the functional relationship of key components of lipid signalling in spermatozoa. Sperm viability and motility of the samples were evaluated by the hypo-osmotic swelling (HOS) test and computer-aided sperm analysis (CASA). Statistical differences between groups were determined using ANOVA and Tukey's test. Normal distribution of the data and variance homogeneity were assessed using Shapiro-Wilk and Levene's test, respectively. A difference was considered significant when the P-value was ≤0.05. S1P mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1. We found that S1PR1 redistributes to the post-acrosomal region upon induction of capacitation. S1P signalling promotes the activation of the PI3K-AKT pathway, leading to NO• production during sperm capacitation. L-NAME, an nitric oxide synthase inhibitor, impaired the Sph- and Cer-dependent capacitation. Additionally, Sph and Cer promote superoxide anion (O2•-) production, and the extracellular addition of superoxide dismutase (SOD) prevented Sph- and Cer-dependent capacitation, suggesting that Sph and Cer stimulate O2•- production during sperm capacitation. Protein kinase type R (PKR), ceramide kinase (CERK), and protein kinase C (PKC) are responsible for translocating and activating sphingosine kinase 1 (SphK1), which is necessary to promote S1P production for sperm capacitation. N/A. The utilization and actions of sphingolipids may differ in spermatozoa of different species. Sphingolipid metabolites such as Sph, Cer, S1P, and ceramide 1-phosphate (C1P) play a crucial role in inducing human sperm capacitation. Our research has provided new insights into fundamental sphingolipid processes in human sperm, including the importance of C1P in translocating and activating SphK1 as well as the S1P signalling to regulate the PI3K/AKT/NOS pathway to generate NO• for sperm capacitation. We are the first to identify the presence of PKR in human spermatozoa and its role in the phosphorylation activities of SphK1 with the subsequent activation of S1P signalling. Furthermore, our study has identified that S1PR1 and S1PR3 are involved in capacitation and the acrosome reaction, respectively. These findings shed light on a novel mechanism by which sphingolipids drive capacitation in human sperm and pave the way for further exploration of the role of bioactive sphingolipid metabolites in this process. Lastly, our studies lay the foundation for examining the lipid profile of infertile males, as potential discrepancies can affect the functional capacity of spermatozoa to reach fertilizing potential. This research was funded by the Canadian Institutes of Health Research (CIHR), grant number PJT-165962 to C.O.F. S.S. was awarded a Research Institute-MUHC Desjardins Studentship. There are no competing interests to report.

Microplastic Particles Detected in Fetal Cord Blood, Placenta, and Meconium: A Pilot Study of Nine Mother-Infant Pairs in South China.

Microplastics (MPs) are emerging environmental pollutants. Pregnancy and infancy are sensitive windows for environmental exposure. However, few studies have investigated the presence of MPs in mother-infant pairs, or the exposure source. In this study, nine mother-infant pairs were recruited, and samples of placenta, cord blood, and meconium were collected. Information about the living environment and dietary habits were collected to determine the source of exposure during pregnancy. Micro-Raman spectroscopy was applied to identify MPs. In total, 9, 4, and 14 types of MPs were identified in the placenta, cord blood, and meconium samples, with particle counts of 34, 14, and 80, respectively. More than 80.47% of MPs detected in samples had a size of 100-400 μm. The abundance of MPs exhibited the order of meconium > placenta > cord blood (Hc = 14.959, p < 0.01). We found that the abundance of MPs in meconium from women who drank tea ≥ 3 times/week during pregnancy was lower than in those who drank less (p = 0.048). Our study presents evidence of MPs transfer via the placenta-cord blood-meconium pathway. We also found that the habit of drinking tea among pregnant women might be related to the abundance of MPs in meconium.

Microplastics in maternal blood, fetal appendages, and umbilical vein blood

Microplastics (MPs) have been detected in placenta and amniotic fluid, but there is no research on whether MPs exist in the other two fetal appendages: fetal membrane and umbilical cord. Additionally, the existence of MPs in umbilical vein blood remains unexplored. Furthermore, it is unclear whether MPs in maternal blood are associated with those in umbilical vein blood and fetal appendages. In this study, we selected 12 full-term pregnant people who delivered by cesarean section, and finally detected 16 kinds of MPs from maternal blood, fetal appendages, and umbilical vein blood by laser direct infrared (LDIR). Polyamide accounted for the highest proportion in the six kinds of samples, followed by Polyurethane. The total MPs median abundance in six kinds of samples were umbilical cord, maternal blood, fetal membrane, amniotic fluid, placenta and umbilical vein blood from high to low, and the specific values were 10.397 particles/g, 8.176 particles/g, 6.561 particles/g, 4.795 particles/g, 4.675 particles/g, and 2.726 particles/g respectively. Moreover, more than 90 % of MPs measured between 20 and 100 μm in diameter. We also found that MPs abundance in amniotic fluid increased with the increase of maternal age (R=0.64, p=0.025) and body mass index before pregnancy (r = 0.59, p= 0.049). However, no statistically significant association was found between lifestyle factors and MPs abundance. Future studies should aim to expand the sample size for further investigation.

Impact of Fetal Umbilical Cord Blood CD34+ Cells on Breast Cancer Cell Lines: A Mechanism of Fetal Microchimerism

Introduction: Fetal microchimerism could be involved in the regulation of breast cancer oncogenesis. CD34+ cells could be of a particular interest as up to 12% of the CD34+ population in maternal blood are of fetal origin. The aim of this research was to analyze the impact of umbilical cord blood (UCB) CD34+ on MCF-7 and MDA-MB-231 breast cancer cell lines, in order to uncover novel biological mechanisms and suggest novel treatment options for breast cancer. Methods: UCB CD34+ cells were obtained from healthy women at full-term delivery. Direct cultures were grown with MCF-7 and MDA-MB-231 cells. Proliferation, migration, invasion, and transcriptomic analysis of breast cancer cell lines were compared between cultures exposed and nonexposed to UCB CD34+ cells. Interactions between UCB CD34+ and breast cancer cells were analyzed under fluorescent microscopy. Functional analyses were generated with QIAGEN’s Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Results: Direct contact between UCB CD34+ and breast cancer cell lines induced a reduction in the proliferative capacities of MCF-7 and MDA-MB-231 and diminished the migration abilities of MDA-MB-231 cells. In 3D coculture, UCB CD34+ cells were attracted by tumor spheroids and incorporated into tumor cells. These cell-to-cell interactions were responsible for transcriptome modifications coherent with observed functional modifications. Among the cytokines secreted by UCB CD34+, IFN-γ was identified as a potential upstream regulator responsible for the molecular modifications observed in transcriptomic analysis of MCF-7 breast cancer cells exposed to UCB CD34+ cells, as was IL-17A in MDA-MB-231 cells. Conclusion: Direct cell-to-cell contact induced functional modifications in breast cancer cells. Interactions between UCB CD34+ and breast cancer cells could induce cell fusion and signal transmission via cytokines. Further analysis of direct cell-to-cell interactions should be performed at a molecular level to further understand the potential role of fetal CD34+ cells in breast cancer.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

New Marker in the Umbilical Cord Blood of Fetuses with Fetal Growth Restriction: Serum Sortilin-1 Level

Objective: To determine the role of sortilin in the pathogenesis of fetal growth restriction (FGR) by examining serum sortilin levels in fetal cord blood. Methods: This prospective case-control study was conducted at Ankara Etlik City Hospital between July 2023 and January 2024. Group 1 included 44 pregnant women with late FGR; Group 2 included 44 healthy pregnant women as controls. Results: Umbilical cord blood sortilin levels were significantly higher in the FGR group [2.96 (2.43–4.01)] compared to the control group [2.12 (1.74–3.18)] (p = 0.001). Sortilin levels negatively correlated with APGAR scores at 1 min (r=-0.281, p = 0.008) and 5 min (r=-0.292, p = 0.006). A sortilin threshold of 2.58 ng/ml predicted composite adverse neonatal outcomes with 66.7% sensitivity, 53.1% specificity, and an AUC of 0.652 (95% CI: 0.529–0.775, p = 0.031). Conclusion: This study showed that sortilin levels, which are indicators of oxidation, were higher in the cord blood of newborns with late FGR.

Magnetic resonance imaging diagnosis of abnormal placental cord insertions

IntroductionAbnormal placental cord insertions (APCIs) are significant risk factors for pregnancy complications, encompassing marginal cord insertion (MCI), velamentous cord insertion (VCI), and vasa previa (VP). While ultrasound is the primary imaging modality, its accuracy can be limited by factors such as maternal obesity and fetal positioning. Complementary to ultrasound, magnetic resonance imaging (MRI) offers a more precise visualization of the fetus, placenta, and umbilical cord relationships. This study aims to investigate the diagnostic value of prenatal magnetic resonance imaging (MRI) for APCIs compared with prenatal ultrasound. MethodsWe retrospectively collected data from 613 patients who underwent prenatal placental ultrasound and MRI. Of those who were confirmed as APCIs through surgery or pathology, the prenatal MRI features were compared with prenatal ultrasound. The diagnostic efficacy of prenatal MRI and ultrasound for APCIs was assessed based on the clinicopathological findings. ResultsFifty-six patients were confirmed as APCIs by surgery or pathology, comprising 31 marginal cord insertions (MCIs), 18 velamentous cord insertions (VCIs), 5 vasa previa (VP) cases, and 2 VCI cases combined with VP. Ultrasound examination showed 55.36 % sensitivity (31/56) and 98.38 % specificity (486/494) in diagnosing APCIs, whereas MRI demonstrated 87.50 % sensitivity (49/56) and 98.88 % specificity (531/537). ConclusionFor APCIs complicated by placental location or morphological abnormalities, MRI demonstrates superior diagnostic efficacy compared to ultrasound in late pregnancy.

A Pilot Study of Ultrasound Assessment of Umbilical Cord and Placental Vascular Flow for Cord Accident Stillbirth Prevention.

Our objective was to determine the feasibility and interobserver reliability of umbilical cord and placental arteriolar flow assessment in low-risk pregnancies near term. This was a prospective pilot study in low-risk pregnancies at 36 weeks with anterior placentas. We excluded any with an indication for antenatal testing or delivery before 39 weeks. Each participant underwent two ultrasounds by different examiners, which included arterial and venous velocimetry at three cord sites (fetal, free loop, and placental) in addition to maternal and fetal placental arterioles. The interobserver reliability was quantified using the Pearson correlation coefficient with that of standard clinical parameters serving as a benchmark for interpretation. Among 53 participants scanned at 356/7-371/7 weeks, the mean examination duration was 20.5 ± 4.2 minutes. Ascertainment success was high for measures at the free loop, placental cord insertion, and fetal placental arterioles (range 90.6%-99.1%) and was lower at the fetal cord insertion and maternal spiral arterioles (range 47.2%-87.7%). Interobserver reliability estimates for free-loop systolic/diastolic and pulsatility index ranged from 0.38 to 0.44. Interobserver reliability for experimental parameters varied by measurement site, and all were poor at the fetal insertion and in placental arterioles. Parameters had significant variation across cord sites (range 4.3%-21.7%). In our cohort, flow assessments of the free loop, placental insertion, and placental arterioles are feasible, but interrater reliability varies by measurement type and cord site. Future studies are needed to establish feasibility and reliability in nonanterior placentation and to assess clinical relevance.

Unveiling the human fetal-maternal interface during the first trimester: biophysical knowledge and gaps.

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes.

Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection.

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations. This study compares three humanized (hu) NOD-derived mouse models for dengue virus-2 (DENV-2) infection in the context of human cytokine expression. Three mouse strains (hu-NSG, hu-EXL, and hu-SGM3) received xenotransplants of human CD34+ fetal cord blood cells from a single donor, and one mouse strain received human peripheral blood mononuclear cells (hu-SGM3-PBMCs). All models exhibited infectious viruses in blood confirmed by plaque assay, but mice expressing human cytokines showed higher viremia compared to conventional NSG mice. The hu-SGM3-PBMCs model developed lethal infections, showing a significant increase in viremia and clinical signs. A detectable human cytokine response was observed in all the DENV-2-infected humanized mouse models. In conclusion, humanized NOD-derived mouse models expressing human cytokines offer a relevant platform for the study of dengue pathogenesis and antiviral therapies.

Fluoride-related changes in the fetal cord blood proteome; a pilot study

BackgroundFluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes.ResultsPathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation.ConclusionMaternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

The Effect of Maternal Blood Glucose on Umbilical Cord Blood Fibrinogen in Women With Gestational Diabetes.

Gestational diabetes mellitus (GDM) is delineated by the presence of glucose intolerance at any level that manifests or is initially identified during pregnancy. Factor I fibrinogen is among the most essential blood coagulation proteins. The concentration of fibrinogen influences platelet aggregation and blood viscosity. This study aimed to determine the correlation between fetal cord blood fibrinogen and plasma fibrinogen in pregnant women with GDM and between fetal cord blood fibrinogen and maternal blood sugar. A cross-sectional study was executed at Al-Elwiya Maternity Teaching Hospital in the obstetrics and gynecology department. The sample included 90 term pregnant women: 45 were confirmed to have GDM, and 45 healthy pregnant women served as control. Estimation of prelabor maternal fasting and random plasma glucose and plasma fibrinogen was performed. During delivery, blood was drawn from the umbilical cord to estimate neonatal plasma glucose and fibrinogen levels. The mean maternal plasma fibrinogen level exhibited a notable increase in women with GDM compared to the control (330.11 ± 56.92 mg/dl versus 254.89 ± 41.01 mg/dl). The infants of diabetic mothers had significantly lower mean cord plasma glucose levels (65.71 ± 14.63 mg/dl versus 77.80 ± 7.81 mg/dl) and higher mean cord plasma fibrinogen levels (269.42 ± 25.91 mg/dl versus 229.69 ± 21.29 mg/dl). Umbilical cord plasma fibrinogen was correlated positively with maternal plasma sugar and fibrinogen. A positive correlation between maternal and fetal cord fibrinogen levels was determined in women with GDM. Monitoring plasma fibrinogen levels in neonates of mothers with GDM could be facilitated by longitudinal, large-scale validation studies enabled by artificial intelligence as a new, evolving technique that contributes to more valuable outcomes. This would shed additional light on the course and function of plasma fibrinogen for a more comprehensive analysis of the fetal clotting system.

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123=74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.

Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25–30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control’s DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.

MYCT1 controls environmental sensing in human haematopoietic stem cells

The processes that govern human haematopoietic stem cell (HSC) self-renewal and engraftment are poorly understood and challenging to recapitulate in culture to reliably expand functional HSCs1–3. Here we identify MYC target 1 (MYCT1; also known as MTLC) as a crucial human HSC regulator that moderates endocytosis and environmental sensing in HSCs. MYCT1 is selectively expressed in undifferentiated human haematopoietic stem and progenitor cells (HSPCs) and endothelial cells but becomes markedly downregulated during HSC culture. Lentivirus-mediated knockdown of MYCT1 prevented human fetal liver and cord blood (CB) HSPC expansion and engraftment. By contrast, restoring MYCT1 expression improved the expansion and engraftment of cultured CB HSPCs. Single-cell RNA sequencing of human CB HSPCs in which MYCT1 was knocked down or overexpressed revealed that MYCT1 governs important regulatory programmes and cellular properties essential for HSC stemness, such as ETS factor expression and low mitochondrial activity. MYCT1 is localized in the endosomal membrane in HSPCs and interacts with vesicle trafficking regulators and signalling machinery. MYCT1 loss in HSPCs led to excessive endocytosis and hyperactive signalling responses, whereas restoring MYCT1 expression balanced culture-induced endocytosis and dysregulated signalling. Moreover, sorting cultured CB HSPCs on the basis of lowest endocytosis rate identified HSPCs with preserved MYCT1 expression and MYCT1-regulated HSC stemness programmes. Our work identifies MYCT1-moderated endocytosis and environmental sensing as essential regulatory mechanisms required to preserve human HSC stemness. Our data also pinpoint silencing of MYCT1 as a cell-culture-induced vulnerability that compromises human HSC expansion.

Atrazine disorganises laminin formation and reduces cell numbers in the tammar testis during early differentiation.

Atrazine, like oestrogen, disorganises laminin formation and reduces the number of germ cells and Sertoli cells in the developing testes of the tammar wallaby. This study suggests that interfering with the balance of androgen and oestrogen affects the integrity of laminin structure and testis differentiation. The herbicide atrazine was banned in Europe in 2003 due to its endocrine disrupting activity but remains widely used. The integrity of the laminin structure in fetal testis cords requires oestrogen signalling but overexposure to xenoestrogens in the adult can cause testicular dysgenesis. However, whether xenoestrogens affect laminin formation in developing testes has not been investigated. Here we examined the effects of atrazine in the marsupial tammar wallaby during early development and compare it with the effects of the anti-androgen flutamide, oestrogen, and the oestrogen degrader fulvestrant. The tammar, like all marsupials, gives birth to altricial young, allowing direct treatment of the developing young during the male programming window (day 20-40 post partum (pp)). Male pouch young were treated orally with atrazine (5 mg/kg), flutamide (10 mg/kg), 17β-oestradiol (2.5 mg/kg) and fulvestrant (1 mg/kg) daily from day 20 to 40 pp. Distribution of laminin, vimentin, SOX9 and DDX4, cell proliferation and mRNA expression of SRY, SOX9, AMH, and SF1 were examined in testes at day 50 post partum after the treatment. Direct exposure to atrazine, flutamide, 17β-oestradiol, and fulvestrant all disorganised laminin but had no effect on vimentin distribution in testes. Atrazine reduced the number of germ cells and Sertoli cells when examined at day 40-50 pp and day 20 to 40 pp, respectively. Both flutamide and fulvestrant reduced the number of germ cells and Sertoli cells. Atrazine also downregulated SRY expression and impaired SOX9 nuclear translocation. Our results demonstrate that atrazine can compromise normal testicular differentiation during the critical male programming window.