Preeclampsia and transport of ions and small molecules: A literature review.

Preeclampsia (PE) is a prevalent obstetric complication affecting approximately 3-5% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality. Preeclampsia is considered a disease of the endothelial system that can progress to eclampsia, characterized by seizures. Early diagnosis and appropriate management are crucial to improving maternal and fetal outcomes, as preeclampsia can lead to severe complications such as placental abruption, fetal growth restriction, and stroke. The pathophysiology of PE is complex, involving a combination of genetic, acquired, and immunological factors. A central feature of the condition is inadequate placentation and impaired uteroplacental perfusion, leading to local hypoxia, endothelial dysfunction, vasoconstriction, and immunological dysregulation. Recent evidence suggests that dysregulation of ion transporters may play a significant role in the adaptation of uterine circulation during placentation. These transporters are essential for maintaining maternal-fetal homeostasis, influencing processes such as nutrient exchange, hormone synthesis, trophoblast cell migration, and the function of smooth muscle cells in blood vessels. In preeclampsia, adverse conditions like hypoxia and oxidative stress result in the downregulation of ion, solute, and water transporters, impairing their function. This review focuses on membrane transporters involved in PE, discussing functional alterations and their physiological implications. The goal of this investigation is to enhance understanding of how dysregulation of ion and small molecule transporters contributes to the development and progression of preeclampsia, underscoring the importance of exploring these signaling pathways for potential therapeutic interventions.

El embarazo gemelar monocorial desde la perspectiva de la teoría de la complejidad / Monochorionic twin pregnancy from the perspective of the theory of complexity

En la práctica, es muy frecuente asociar las gestaciones gemelares monocoriales (MC) con embarazos complejos o complicados, utilizando ambos términos en forma intercambiable. Sin embargo, no lo son; el dinamismo es protagonista en los sistemas complejos, pero no en los complicados. Para entender a la embarazada con una gestación MC como un sistema complejo, primero se desarrollarán las características principales de los embarazos MC; su placenta es una de las principales responsables de los problemas. Luego se analizará el embarazo MC desde la complejidad, identificando las características del sistema y sus complicaciones como propiedades emergentes.

In practice, it is very common to associate monochorionic (MC) twin pregnancies with complex or complicated pregnancies, using both terms interchangeably. However, these are not synonyms; dynamism is the protagonist in complex systems, but not in complicated ones. In order to understand a MC pregnancy as a complex system, it is necessary to first look into its main characteristics. The placenta is one of the main sources of problems. Then, the MC pregnancy has to be analyzed from the perspective of complexity, identifying the system characteristics and its complications as emergent properties.

Rentabilidad de la ratio angiogénica en el seguimiento de gestantes de alto riesgo de preeclampsia precoz tratadas con ácido acetilsalicílico / Profitability of the angiogenic ratio in the follow-up of pregnant women at high risk of early preeclampsia treated with acetylsalicylic acid

Objetivo: Evaluar el valor predictivo negativo de la ratio antigénica y conocer su rentabilidad para descartar preeclampsia precoz en pacientes de alto riesgo de desarrollarla, con profilaxis de ácido acetilsalicílico. Métodos: Se realizó un estudio descriptivo transversal que recogió a las gestantes con cribado de preeclampsia precoz de alto riesgo (384 gestantes) en el Hospital Santa Lucía durante el año 2021, para lo que se usó test Elecsys® tabulado a un riesgo mayor a 1/150 en primer trimestre, y que tomaran ácido acetilsalicílico antes de la semana 16, quedando en 368 gestantes vistas en las semanas 20, 26, 31 y 36. Se realizó biometría, ratio angiogénica y doppler. Resultados: La incidencia de preeclampsia precoz en la población fue 4 casos (incidencia 1,08 %). Son significativos por su alto valor predictivo negativo del 100 % de preeclampsia precoz: la ratio angiogénica mayor a 38 en la semana 26 y el doppler de las uterinas en semana 20 y 26. Conclusión: En gestaciones con cribado de alto riesgo de preeclampsia que tomen ácido acetilsalicílico, una ratio angiogénica menor a 38 en la semana 26, además de un doppler uterino normal en semana 20 y 26 permite reducir el seguimiento gestacional(AU)

Objective: Our main objective was to evaluate the negative predictive value of the angiogenic ratio and to know its profitability to rule out early preeclampsia in patients at high risk of early preeclampsia with acetylsalicylic acid prophylaxis. Methods: A cross-sectional descriptive study was carried out that included pregnant women with high-risk early preeclampsia screening (384 pregnant women) at the Santa Lucía Hospital during the year 2021, for which the Elecsys® test tabulated at a risk >1/ was used. 150 in the first trimester, and who take acetylsalicylic acid before week 16, leaving 368 pregnant women seen in weeks 20, 26, 31 and 36, with biometry, angiogenic ratio and Doppler performed. Results: The incidence of early preeclampsia in the population was 4 cases (incidence 1.08%). They are significant due to their high negative predictive value of 100% of early preeclampsia: Angiogenic ratio > 38 in week 26, uterine Doppler in weeks 20 and 26. Conclusion: Pregnancies with high risk screening for preeclampsia who take acid acetylsalicylic acid, an angiogenic ratio < 38 at week 26 in addition to a normal uterine Doppler at weeks 20 and 26 allows for reduced gestational follow-up(AU)

Overexpression of long noncoding RNA DUXAP8 inhibits ER-phagy through activating AKT/mTOR signaling and contributes to preeclampsia.

Preeclampsia (PE) is a life-threatening pregnancy-specific complication with controversial mechanisms and no effective treatment except delivery is available. Currently, increasing researchers suggested that PE shares pathophysiologic features with protein misfolding/aggregation disorders, such as Alzheimer disease (AD). Evidences have proposed defective autophagy as a potential source of protein aggregation in PE. Endoplasmic reticulum-selective autophagy (ER-phagy) plays a critical role in clearing misfolded proteins and maintaining ER homeostasis. However, its roles in the molecular pathology of PE remain unclear. We found that lncRNA DUXAP8 was upregulated in preeclamptic placentae and significantly correlated with clinical indicators. DUXAP8 specifically binds to PCBP2 and inhibits its ubiquitination-mediated degradation, and decreased levels of PCBP2 reversed the activation effect of DUXAP8 overexpression on AKT/mTOR signaling pathway. Function experiments showed that DUXAP8 overexpression inhibited trophoblastic proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Moreover, pathological accumulation of swollen and lytic ER (endoplasmic reticulum) was observed in DUXAP8-overexpressed HTR8/SVneo cells and PE placental villus trophoblast cells, which suggesting that ER clearance ability is impaired. Further studies found that DUXAP8 overexpression impaired ER-phagy and caused protein aggregation medicated by reduced FAM134B and LC3II expression (key proteins involved in ER-phagy) via activating AKT/mTOR signaling pathway. The increased level of FAM134B significantly reversed the inhibitory effect of DUXAP8 overexpression on the proliferation, migration, and invasion of trophoblasts. In vivo, DUXAP8 overexpression through tail vein injection of adenovirus induced PE-like phenotypes in pregnant rats accompanied with activated AKT/mTOR signaling, decreased expression of FAM134B and LC3-II proteins and increased protein aggregation in placental tissues. Our study reveals the important role of lncRNA DUXAP8 in regulating trophoblast biological behaviors through FAM134B-mediated ER-phagy, providing a new theoretical basis for understanding the pathogenesis of PE.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

A Narrative Review on the Pathophysiology of Preeclampsia.

Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.

Advancing Neurosurgical Skills: A Comparative Study of Training Models for Intra-Extracranial Cerebral Bypass.

BACKGROUND: Training in anastomosis is fundamental in neurosurgery due to the precision and dexterity required. Biological models, although realistic, present limitations such as availability, ethical concerns, and the risk of biological contamination. Synthetic models, on the other hand, offer durability and standardized conditions, although they sometimes lack anatomical realism. This study aims to evaluate and compare the efficiency of anastomosis training models in the intra-extracranial cerebral bypass procedure, identifying those characteristics that enhance optimal microsurgical skill development and participant experience. METHODS: A neurosurgery workshop was held from March 2024 to June 2024 with 5 vascular techniques and the participation of 22 surgeons. The models tested were the human placenta, the Wistar rat, the chicken wing artery, the nasogastric feeding tube, and the UpSurgeOn Mycro simulator. The scales used to measure these models were the Main Characteristics Score and the Evaluation Score. These scores allowed us to measure, qualitatively and quantitatively, durability, anatomical similarity, variety of simulation scenarios, risk of biological contamination, ethical considerations and disadvantages with specific infrastructure. RESULTS: The human placenta model, Wistar rat model, and UpSurgeOn model were identified as the most effective for training. The human placenta and Wistar rat models were highly regarded for anatomical realism, while the UpSurgeOn model excelled in durability and advanced simulation scenarios. Ethical and cost implications were also considered. CONCLUSIONS: The study identifies the human placenta and UpSurgeOn models as optimal for training in intra-extracranial bypass procedures, emphasizing the need for diverse and effective training models in neurosurgery.

Sex-specific effect of antenatal Zika virus infection on murine fetal growth, placental nutrient transporters, and nutrient sensor signaling pathways.

Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient-sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU-ZIKVPE243) or High (5 × 107 PFU-ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal-placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho-eIF2α. There were no differences in fetal-placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose-6-phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium-coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex-dependent differences in the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation in ZIKV-infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV-induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome.

Manganese porphyrin-based treatment improves fetal-placental development and protects against oxidative damage and NLRP3 inflammasome activation in a rat maternal hypothyroidism model.

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1ß, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.

Placental apoptosis increased by hypoxia inducible factor-1 stabilization is counteracted by leptin†.

During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed toward the relevance of hypoxia as modulator of trophoblast cell death. Previous reports have shown that leptin, a placental cytokine, promotes cell survival in both cell culture and placental explant models. The aim of this work is to establish the role of leptin in apoptosis under hypoxic condition in trophoblast cells. In this study, we evaluated the effect of cobalt chloride, a hypoxia mimicking agent that stabilizes the expression of hypoxia-inducible factor-1 alpha, on Swan-71 and human placental explants. Hypoxia chamber was also used to generate 2% oxygen. Apoptosis was determined by the presence of apoptotic nucleus, fragmentation of DNA and Caspase-3 and PARP-1 cleavage. The pro-apoptotic proteins BAX, BID, BAD, and BAK and the anti-apoptotic effectors BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1 were also analyzed. We found that hypoxia-inducible factor-1 alpha stabilization increased the appearance of apoptotic nucleus, fragmentation of DNA, and Caspase-3 and PARP-1 cleavage. Hypoxia mimicking conditions enhanced the expression of pro-apoptotic effectors BAX, BID, BAD, and BAK. Hypoxia-inducible factor-1 alpha stabilization also downregulated the level of BCL-2, B-cell lymphoma-extra-large, and myeloid cell leukemia-1. All these apoptotic parameters changes were reversed with leptin treatment. Moreover, we showed that leptin action on apoptosis modulation involves PI3K and MAPK signaling pathways. Obtained data demonstrate that hypoxia-inducible factor-1 alpha stabilization induces apoptosis in human placenta and leptin counteracts this effect, reinforcing its role as a survival cytokine.

Evaluation of embryo-foetal biometry and its correlation with parturition date in Toy Poodle bitches.

Estimating the parturition date in dogs is challenging due to their reproductive peculiarities that. Ultrasonographic examination serves as a tool for studying embryo/foetal biometry and estimating the time of parturition by measuring foetal and extra-foetal structures. However, due to reproductive differences among various dog breeds, such estimates may have a non-significant pattern, representing inaccuracies in the estimated date of birth. This study aimed to monitor pregnant Toy Poodle bitches and establish relationships between ultrasonographically measured foetal and extra-foetal dimensions and the remaining time until parturition. Eighteen pregnant Toy Poodle bitches were subjected to weekly ultrasonographic evaluations and measurements of the inner chorionic cavity diameter, craniocaudal length (CCL), biparietal diameter (BPD), diameter of the deep portion of diencephalo-telencephalic vesicle (DPTV), abdominal diameter, thorax diameter (TXD), placental thickness and the renal diameter (REND). These parameters were retrospectively correlated with the date of parturition and linear regressions were established between gestational measurements and days before parturition (DBP). All analyses were conducted using the Statistical Package for Social Sciences (IBM® SPSS®) program at a 5% significance level. The foetal measurements that showed a high correlation (r) and reliability (R2) with DBP were BPD [(DBP = [15.538 × BPD] - 39.756), r = .97 and R2 = .93], TXD [(DBP = [8.933 × TXD] - 32.487), r = .94 and R2 = .89], DPTV [(DBP = [34.580 × DPTV] - 39.403), r = .93 and R2 = .86] and REND [(DBP = [13.735 × REND] - 28.937), r = .91 and R2 = .82]. This statistically validates the application of these specific formulas to estimate the parturition date in Toy Poodle bitches.

Assessing the risks for stillbirth in São Paulo, Brazil: protocol for a multidisciplinary case-control study - FetRisks.

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.

Association between maternal and perinatal outcomes and histological changes in the placenta of patients with Covid-19: A cohort study.

Although studies evaluated placental involvement in Covid-19 patients, few have assessed its association with clinical repercussions. The study aimed to determine the association between the clinical status and maternal and perinatal outcomes of patients with Covid-19 at delivery and changes in placental histology. It is so far the largest cohort evaluating placentas of patients infected by the SARS-CoV-2. A secondary analysis was conducted of a database from which a cohort of 226 patients, who tested real-time polymerase chain reaction-positive for Covid-19 at delivery and whose placentas were collected and submitted to pathology, was selected for inclusion. One or more types of histological changes were detected in 44.7% of the 226 placentas evaluated. The most common abnormalities were maternal vascular malperfusion (38%), evidence of inflammation/infection (9.3%), fetal vascular malperfusion (0.8%), fibrinoid changes and intervillous thrombi (0.4%). Oxygen use (P = .01) and need for admission to an intensive care unit (ICU) (P = .04) were less common in patients with placental findings, and hospital stay was shorter in these patients (P = .04). There were more fetal deaths among patients with evidence of inflammation/infection (P = .02). Fetal death, albeit uncommon, is associated with findings of inflammation/infection. Oxygen use and need for admission to an ICU were less common among patients with placental findings, probably due to the pregnancy being interrupted early. None of the other findings was associated with maternal clinical status or with adverse perinatal outcome.

Bovine papillomavirus vertical transmission: BPV diversity and expression in maternal and fetal tissues.

Bovine Papillomaviruses (BPVs) constitute a diverse group within the Papillomaviridae family, playing a crucial role in bovine health and economic considerations. This study investigates the dynamics of vertical transmission of BPV in cattle, focusing on five cows and their reproductive tissues, as well as three gravid cows and their fetuses. DNA and RNA samples were extracted from the warts, fetal skin, placenta, uterus, ovary, and blood of cows, as well as the skin and blood of fetuses. Polymerase Chain Reaction (PCR) targeted BPV types 1-6 and 8-14, was assessed in both cows and fetuses. Additionally, Reverse Transcription PCR (RT-PCR) examined BPV-2 E5 oncogene expression in the skin and reproductive sites of mother cows and fetuses. Our findings unveil a rich diversity of BPV types, including BPV-2, 3, 9, 10, 12, and 14, present in both maternal and fetal tissues. Intriguingly, certain types, namely BPV-4, 6, 8, and 11, were exclusively identified in maternal tissues A higher diversity of BPVs was observed in cow warts, followed by cow blood, fetal blood, and fetal skin. Strikingly similar BPV types in gravid cow blood and fetuses suggest primary dissemination through the bloodstream and transmission via the placenta, though detected in lower numbers in cow uterus and ovary. Histopathological analysis revealed no abnormalities in the reproductive tissues despite the presence of BPV. However, in one bladder sample from a cow that did not consume bracken fern, urothelial neoplasia in situ was observed. The study extends beyond detection, exploring the expression of the BPV-2 E5 oncogene in fetal tissues, providing insights into potential cell implications. Comparative analyses with previous studies highlight the uniqueness of our investigation, encompassing a broader array of BPV types in the gravid cows and their fetuses. The findings not only establish a foundation for further investigations into the mechanisms of vertical transmission but also highlight the need for targeted interventions and surveillance strategies to mitigate potential health risks associated with specific BPV types.

Online scientific research on placentophagy: a bibliometric analysis.

Objective: To classify the bibliometric indicators of online scientific research on placentophagy. Methods: A bibliometric study was conducted to quantify the scientific production of authors and institutions with the aim of highlighting the growth and impact of these publications nationally and internationally. The Bradford Law, network maps, and textual statistics were used, with searches conducted in libraries and databases in October 2021. Results: The sample consisted of 64 articles, whose primary authors were associated with 49 institutions, and mostly with degrees in anthropology. The United States of America was the country that published the most papers on the theme, and most studies were reviews with individual production. Through the term analysis, it was found that the predominant themes regarding placentophagy were the following: Alternative therapy for women's health, methodologies used for research in this area, period of placenta ingestion (postpartum period), and its benefits. Conclusion: The bibliometric indicators found are essential for the development of future research.

Association of placental histopathological findings with COVID-19 and its predictive factors.

Objective: The aims of the study are to describe the association of coronavirus disease (COVID-19) with the abnormal histopathological findings in human placenta and to highlight the potential predictors of these histopathological findings. Methods: A retrospective cohort study, held in two obstetric units from January 2021- 2022, 34 patients who were confirmed cases of COVID- 19 were followed up till the time of delivery as their placenta were sent for histopathology. Patients diagnosed with other viral infections, chorioamnionitis, or were known case of as pre-term or term pre labour rupture of membrans (PROM) were excluded as well as pre exisiting diabetes mellitus or pre-eclampsia. Data analysis were performed using STATA software version 16. Result: Specific histopatological findings (fetal vascular malperfusion, maternal vascular malperfusion, inflammatory pathology and thrombotic finding) were significantly high among 13 (38.2%) of the study group who got infected earlier in pregnancy (P<0.001). The period between the diagnosis of COVID-19 and the delivery significantly increases the odds of the presence of pathological findings by 2.75 times for each week the patients getting infected earlier. Conclusion: Association of abnormal placental histopathological findings with COVID-19 infection in pregnancy and the potential predictor for the occurrence of placental findings is the longer duration between the diagnosis of the infection and the delivery.

Plasmodium falciparum alters the trophoblastic barrier and stroma villi organization of human placental villi explants.

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.

Placental abnormalities associated with Leptospira interrogans infection in naturally infected mares.

The reproductive features of equine leptospirosis are often neglected. Equine genital leptospirosis is characterized as a silent chronic syndrome, and besides abortions, leads to placental abnormalities, stillbirths, and birth of weak foals. This study aimed to study the occurrence of placental abnormalities associated with Leptospira interrogans infection in naturally infected mares under field conditions. The studied herd had a high occurrence of placentitis and abortions. Ten pregnant mares, eight with placental abnormalities on ultrasonography and were selected. Serum and cervicovaginal mucus (CVM) samples were collected for serology and PCR, respectively. Positive samples in lipL32-PCR were submitted to the sequencing of the secY gene. In lipL32-PCR of CVM, five out of 10 (50%) mares were positive and all were characterized as Leptospira interrogans. Our results highlight the presence of placental abnormalities in the reproductive subclinical leptospirosis syndrome. We encourage field veterinarians to include leptospirosis testing in their reproductive management.

Morphological and clinical findings in placentas and newborns with a history of tobacco, alcohol, and other substance abuse during pregnancy.

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.