Search Results (19)

Prepartum vaccination of dairy cows against newborn calf diarrhea protects calves during the first weeks of life via the colostrum. Vaccination may also induce non-specific effects (NSEs) beyond antibody production, altering the disease susceptibility and productivity of the vaccinated mother. This retrospective study analyzed herd records and on-site survey data from 73,378 dairy cows on 20 German farms using linear mixed-effects models and random forest algorithms. Management practices and milk yield showed stronger associations with outcomes than vaccination. However, the cows vaccinated with non-live vaccines had increased odds of retained placenta and metritis (OR: 1.5–1.7), as well as endometritis (OR: 3–6), and were 20–24% less likely to conceive than non-vaccinated cows. Among non-live vaccinated cows, those vaccinated 2.5–4 weeks before calving had an 8% higher non-return rate compared to those vaccinated 6–8 weeks prior. Multiparous cows receiving live vaccine components were 1.9 times more likely to conceive, compared to non-live vaccinated multiparous cows. These findings suggest potential NSE of prepartum vaccination on uterine health and fertility. However, this study’s retrospective design limits causal interpretation, and the benefits in calves may outweigh possible adverse effects. Further research should clarify the mechanisms and optimize vaccine timing and composition. Full article

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations. Full article

The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above gap, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women immediately after term delivery, seven of which had SARS-CoV-2 infection confirmed by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We separately extracted total RNA from placental tissues from maternal and fetal compartments, constructed cDNA libraries, and sequenced them to assess mRNA. Our analysis revealed 635 differentially expressed genes when a false discovery rate (FDR ≤ 0.05) was applied in the maternal placental tissue, with 518 upregulated and 117 downregulated genes in the SARS-CoV-2-positive women (n = 6) compared with the healthy SARS-CoV-2-negative women (n = 8). In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. We observed a significant downregulation of nine genes belonging to the pregnancy-specific glycoprotein related to the immunoglobulin superfamily in the maternal compartment with active SARS-CoV-2 infection (fold change range from −13.70 to −5.28; FDR ≤ 0.01). Additionally, comparing symptomatic women with healthy women, we identified 1788 DEGs. Furthermore, a signaling pathway enrichment analysis revealed that pathways related to oxidative phosphorylation, insulin secretion, cortisol synthesis, estrogen signaling, oxytocin signaling, antigen processing, and presentation were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risks of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta’s anti-viral effects in maternal SARS-CoV-2 infection. Full article

The aim of this review was to examine the current literature regarding the effect of maternal lifestyle interventions (i.e., diet and physical activity) on the epigenome of the offspring. PubMed, Scopus and Cochrane-CENTRAL were screened until 8 July 2023. Only randomized controlled trials (RCTs) where a lifestyle intervention was compared to no intervention (standard care) were included. Outcome variables included DNA methylation, miRNA expression, and histone modifications. A qualitative approach was used for the consideration of the studies’ results. Seven studies and 1765 mother–child pairs were assessed. The most common types of intervention were dietary advice, physical activity, and following a specific diet (olive oil). The included studies correlated the lifestyle and physical activity intervention in pregnancy to genome-wide or gene-specific differential methylation and miRNA expression in the cord blood or the placenta. An intervention of diet and physical activity in pregnancy was found to be associated with slight changes in the epigenome (DNA methylation and miRNA expression) in fetal tissues. The regions involved were related to adiposity, metabolic processes, type 2 diabetes, birth weight, or growth. However, not all studies showed significant differences in DNA methylation. Further studies with similar parameters are needed to have robust and comparable results and determine the biological role of such modifications. Full article

Planned out-of-hospital births, facilitated by highly skilled and experienced midwives, offer expectant parents a distinct opportunity to partake in a personalized, intimate, and empowering birth experience. Many parents opt for the care provided by midwives who specialize in supporting home births. This retrospective study is based on 41,335 EMS emergency calls to women in advanced pregnancy, of which 209 concerned home birth situations documenting obstetrical emergencies over four years (January 2018 to December 2022), of which 60 involved the assistance of a midwife. Data were obtained from the Polish Central System for Emergency Medical Services Missions Monitoring, encompassing all EMS interventions in pregnant women. The most frequent reason for emergency calls for obstetrical emergencies with the assistance of a midwife was a failure to separate the placenta or incomplete afterbirth (18 cases; 30%), followed by perinatal haemorrhage (12 cases; 20%) and deterioration of the newborn’s condition (8 cases; 13%). Paramedic-staffed EMS teams conducted most interventions (43 cases; 72%), with only 17 (28%) involving the presence of a physician. Paramedics with extensive medical training and the ability to provide emergency care are in a unique position that allows them to play a pivotal role in supporting planned out-of-hospital births. The analysed data from 2018–2022 show that EMS deliveries in Poland are infrequent and typically uncomplicated. Continuing education, training, and adequate funding are required to ensure the EMS is ready to provide the best care. EMS medical records forms should be adapted to the specific aspects of care for pregnant patients and newborns. Full article

Today, there is strong and diversified evidence that in humans at least 50% of early embryos do not proceed beyond the pre-implantation period. This evidence comes from clinical investigations, demography, epidemiology, embryology, immunology, and molecular biology. The purpose of this article is to highlight the steps leading to the establishment of pregnancy and placenta formation. These early events document the existence of a clear distinction between embryonic losses during the first two weeks after conception and those occurring during the subsequent months. This review attempts to highlight the nature of the maternal–embryonic dialogue and the major mechanisms active during the pre-implantation period aimed at “selecting” embryos with the ability to proceed to the formation of the placenta and therefore to the completion of pregnancy. This intense molecular cross-talk between the early embryo and the endometrium starts even before the blastocyst reaches the uterine cavity, substantially initiating and conditioning the process of implantation and the formation of the placenta. Today, several factors involved in this dialogue have been identified, although the best-known and overall, the most important, still remains Chorionic Gonadotrophin, indispensable during the first 8 to 10 weeks after fertilization. In addition, there are other substances acting during the first days following fertilization, the Early Pregnancy Factor, believed to be involved in the suppression of the maternal response, thereby allowing the continued viability of the early embryo. The Pre-Implantation Factor, secreted between 2 and 4 days after fertilization. This linear peptide molecule exhibits a self-protective and antitoxic action, is present in maternal blood as early as 7 days after conception, and is absent in the presence of non-viable embryos. The Embryo-Derived Platelet-activating Factor, produced and released by embryos of all mammalian species studied seems to have a role in the ligand-mediated trophic support of the early embryo. The implantation process is also guided by signals from cells in the decidualized endometrium. Various types of cells are involved, among them epithelial, stromal, and trophoblastic, producing a number of cellular molecules, such as cytokines, chemokines, growth factors, and adhesion molecules. Immune cells are also involved, mainly uterine natural killer cells, macrophages, and T cells. In conclusion, events taking place during the first two weeks after fertilization determine whether pregnancy can proceed and therefore whether placenta’s formation can proceed. These events represent the scientific basis for a clear distinction between the first two weeks following fertilization and the rest of gestation. For this reason, we propose that a new nomenclature be adopted specifically separating the two periods. In other words, the period from fertilization and birth should be named “gestation”, whereas that from the completion of the process of implantation leading to the formation of the placenta, and birth should be named “pregnancy”. Full article

Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that RTL5 and RTL6 (also known as sushi-ichi retrotransposon homolog 8 (SIRH8) and SIRH3) are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of RTL9 (also known as SIRH10). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that RTL9 plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in Rtl9 knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: RTL9, RTL5 and RTL6, responding to fungi, viruses and bacteria, respectively. Full article

Recent advances in high-throughput in silico techniques translate experimental data into meaningful biological networks through which the role of individual proteins, interactions, and their biological functions are comprehended. The study objective was to identify differentially expressed (DE) miRNAs between the day 16 competent, elongated embryo from normal cows and the day 16 noncompetent, tubular embryos from repeat breeder cows, assimilate DE-miRNAs to their target genes, and group target genes based on biological function using in silico methods. The 84 prioritized bovine-specific miRNAs were investigated by RT-PCR, and the results showed that 19 were differentially expressed (11 up- and 8 down-regulated) in the competent embryos compared to noncompetent ones (p ≤ 0.05; fold regulation ≥ 2 magnitudes). Top-ranked integrated genes of DE-miRNAs predicted various biological and molecular functions, cellular processes, and signaling pathways. Further, analysis of the categorized groups of genes showed association with signaling pathways, turning on or off key genes and transcription factors regulating the development of embryo, placenta, and various organs. In conclusion, highly DE-miRNAs in day 16 bovine conceptus regulated the embryogenesis and pregnancy establishment. The elucidated miRNA-mRNA interactions in this study were mostly based on predictions from public databases. Therefore, the causal regulations of these interactions and mechanisms require further functional characterization. Full article

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target. CB-ECFCs exposed to experimental hypoxia demonstrated downregulation of NOX4-mediated reactive oxygen species (ROS) signalling linked with a reduced tube formation, which was partially restored by NOX4 plasmid overexpression. siRNA knockdown of placenta-specific 8 (PLAC8), identified by microarray analysis as an upstream regulator of NOX4 in hypoxic versus normoxic CB-ECFCs, enhanced tube formation, NOX4 expression and hydrogen peroxide generation, and induced several key transcription factors associated with downstream Nrf2 signalling. Taken together, these findings indicated that activation of the PLAC8–NOX4 signalling axis improved CB-ECFC angiogenic functions in experimental hypoxia, highlighting this pathway as a potential target for protecting therapeutic cells against the ischaemic cardiovascular disease microenvironment. Full article

This study aimed to evaluate the accuracy of the thick blood smear (TBS) versus quantitative polymerase chain reaction (qPCR) for the diagnosis of malaria associated with pregnancy (MAP) caused by P. falciparum or P. vivax in Colombia in its gestational malaria (GM), placental malaria (PM), and congenital malaria (CM) forms as well as to compare its accuracy in different subgroups of pregnant women according to the presence of fever, anemia and a history of malaria. This was a diagnostic evaluation of 829 pregnant women, 579 placentas, 381 umbilical cord samples, and 221 neonatal peripheral blood samples. Accuracy was evaluated based on the parameters of sensitivity, specificity, predictive values, likelihood ratios, and validity index, with their 95% confidence intervals. The frequency of GM was 36% (n = 297/829), PM 27% (n = 159/579), and CM 16.5% (n = 63/381) in umbilical cord samples and 2% (n = 5/221) in neonatal peripheral blood samples. For GM, the sensitivity was 55%, with higher rates in those infected with P. vivax (68%), with a history of malaria (69%), and with fever (96%). These three subgroups presented the best results in terms of the negative likelihood ratio and validity index. For PM, sensitivity was 8%; in subgroup analyses in terms of species, symptomatology (anemia and fever), and history of malaria, it was 1–18%, and the negative likelihood ratio was >0.80 in all subgroups. No false positives were recorded in any of the subgroups. The TBS did not detect any cases of CM. This study found the TBS yielded satisfactory results in terms of diagnosing GM for P. vivax, pregnant women with previous malaria and febrile. It also showed that the TBS is not useful for diagnosing PM and CM. It is necessary to conduct surveillance of MAP with molecular methods in in groups where TBS is deficient (asymptomatic GM, P. falciparum, and pregnant women without history of malaria) to optimize the timely treatment of PM and CM, avoid the deleterious effects of MAP and achieve the malaria elimination goals in Colombia. Full article

Fetal growth restriction (FGR) is associated with short- and long-term morbidity, often with fetal compromise in utero, evidenced by abnormal Doppler velocimetry of fetal vessels. Lipids are vital for growth and development, but metabolism in FGR pregnancy, where fetuses do not grow to full genetic potential, is poorly understood. We hypothesize that triglyceride concentrations are increased in placentas and that important complex lipids are reduced in cord plasma from pregnancies producing the smallest babies (birth weight < 5%) and correlate with ultrasound Dopplers. Dopplers (umbilical artery, UA; middle cerebral artery, MCA) were assessed longitudinally in pregnancies diagnosed with estimated fetal weight (EFW) < 10% at ≥29 weeks gestation. For a subset of enrolled women, placentas and cord blood were collected at delivery, fatty acids were extracted and targeted lipid class analysis (triglyceride, TG; phosphatidylcholine, PC; lysophosphatidylcholine, LPC; eicosanoid) performed by LCMS. For this sub-analysis, participants were categorized as FGR (Fenton birth weight, BW ≤ 5%) or SGA “controls” (Fenton BW > 5%). FGRs (n = 8) delivered 1 week earlier (p = 0.04), were 29% smaller (p = 0.002), and had 133% higher UA pulsatility index (PI, p = 0.02) than SGAs (n = 12). FGR plasma TG, free arachidonic acid (AA), and several eicosanoids were increased (p < 0.05); docosahexaenoic acid (DHA)-LPC was decreased (p < 0.01). Plasma TG correlated inversely with BW (p < 0.05). Plasma EET, non-esterified AA, and DHA correlated inversely with BW and directly with UA PI (p < 0.05). Placental DHA-PC and AA-PC correlated directly with MCA PI (p < 0.05). In fetuses initially referred for inadequate fetal growth (EFW < 10%), those with BW ≤ 5% demonstrated distinctly different cord plasma lipid profiles than those with BW > 5%, which correlated with Doppler PIs. This provides new insights into fetal lipidomic response to the FGR in utero environment. The impact of these changes on specific processes of growth and development (particularly fetal brain) have not been elucidated, but the relationship with Doppler PI may provide additional context for FGR surveillance, and a more targeted approach to nutritional management of these infants. Full article

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases (n = 2), whereas 92% of cases were negative (n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted (n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal–neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients. Full article

Background: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. Methods: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. Results: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0.007) but not with the severity of maternal COVID-19 disease. Conclusion: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease. Full article

Recurrent pregnancy loss (RPL) has an estimated incidence of 1–3% of all couples. The etiology is considered to be multifactorial. Extracellular vesicles (EVs) take part in numerous different physiological processes and their contents show the originating cell and pathophysiological states in different diseases. In pregnancy disorders, changes can be seen in the composition, bioactivity and concentration of placental and non-placental EVs. RPL patients have an increased risk of pregnancy complications. The aim of this prospective study was to examine whether measuring different specific EV markers in plasma before and during pregnancy could be used as predictors of pregnancy loss (PL) in women with RPL. Thirty-one RPL patients were included in this study; 25 had a live birth (LB group) and six had a new PL (PL group). Five blood samples were obtained, one before achieved pregnancy and the others in gestational week 6, 8, 10 and 16. Moreover, some of the patients received intravenous immunoglobulin (IVIG) infusions as part of treatment, and it was also examined whether this treatment influenced the EV levels. Seventeen EV markers specific for the immune system, coagulation, placenta and hypoxia were analyzed in the samples with EV Array, a method able to capture small EVs by using an antibody panel targeting membrane proteins. Comparing the LB and PL groups, one EV marker, CD9, showed a significant increase from before pregnancy to gestational week 6 in the PL group. The changes in the other 16 markers were nonsignificant. One case of late-onset PL showed steeply increasing levels, with sudden decrease after gestational week 10 in nine of 17 markers. Moreover, there was an overall increase of all 17 markers after IVIG treatment in the LB group, which was significant in 15 of the markers. Whether increases in EVs positive for CD9 characterize RPL patients who subsequently miscarry should be investigated in future larger studies. Full article

Background. Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value and to determine the most appropriate cut-off values for the prediction of chorioamnionitis. Methods. This case control study included women who were diagnosed with preterm premature rupture of the membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free-leaking amniotic fluid was obtained vaginally with a sterile speculum less than 48h before delivery. Amniotic fluid IL-6, TNF-α, and MMP-8 levels were determined by the Enzyme Linked Immunosorbent Assay. Diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. Results. The study included 156 women, 65 patients in the histological chorioamnionitis group (Group I) and 91 in a group without diagnosed histological chorioamnionitis (Group II). The median concentrations of IL-6, MMP-8, and TNF-α in amniotic fluid were statistically significantly higher in Group I than in Group II (p-value < 0.001). The area under the curve of TNF-α and MMP-8 were higher than the area under the curve of IL-6 (0.91, 0.89, and 0.81, respectively). No statistically significant difference was found when comparing the receiver operating characteristic (ROC) curves of TNF-α and MMP-8. The optimum cut-off values for the prediction of chorioamnionitis were found to be 1389.82 pg/mL for IL-6, 21.17 pg/mL for TNF-α, and 172.53 ng/mL for MMP-8. The sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV) of the IL-6 cut-off for chorioamnionitis were 88%, 70%, 67%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of the TNF-α cut-off were 88%, 84%, 79%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of the MMP-8 cut-off were 80%, 87%, 81%, and 86%, respectively. Conclusions. The vaginally obtained amniotic fluid IL-6, MMP-8, and TNF-α seem to be good predictors for chorioamnionitis of patients with preterm premature rupture of membranes before 34 weeks of gestation. The noninvasive technique of sampling amniotic fluid could be alternative method to invasive amniocentesis. Full article