Search Results (240)

Adequate birth weight is essential for animal survival and subsequent growth. However, the mechanism by which placental DNA methylation influences fetal growth remains incompletely understood. This study employed whole-genome bi-sulfite sequencing (WGBS) and RNA sequencing to analyze placental tissues from two weak piglets and two normal piglets born to the same sow. Transcriptome analysis identified 1989 differentially expressed genes (DEGs) enriched in blood/immune processes. Additionally, differentially methylated regions linked to DEG repression were enriched in extracellular matrix (ECM) receptors and angiogenesis pathways. To investigate the role of DNA methylation in gene regulation, porcine trophoblast cells (PTr2) were treated with either DMSO (control) or the DNA methylation inhibitor 5-Aza-2′-deoxycytidine (5-Aza). Real-time quantitative PCR (RT-qPCR) analysis demonstrated significant upregulation of PACC1, SLC7A1, and PKP1 gene expression in the 5-Aza-treated group compared to controls (p < 0.05). Furthermore, methylation-specific PCR (MS-PCR) assays confirmed that the transcriptional activity of these genes is directly modulated by DNA methylation. These findings suggest that the dynamic regulation of DNA methylation in gene promoters may influence variations in placental morphology and birth weight in piglets, offering new insights into epigenetic regulation of fetal development, though larger studies are needed for validation. Full article

Cardiac disease remains a leading cause of maternal morbidity and mortality, particularly in developed countries where improved survival has increased the number of pregnant patients with congenital heart disease. The physiological changes of pregnancy, such as increased blood volume, cardiac output, and hypercoagulability, can exacerbate preexisting cardiac conditions, posing significant anesthetic challenges during cesarean delivery. This review outlines anesthetic strategies for parturients with structural or functional cardiac disease, emphasizing individualized, multidisciplinary care. We examine general and regional anesthesia approaches, intraoperative monitoring, and hemodynamic goals, including fluid balance, venous return optimization, and myocardial oxygen demand reduction. Preoperative risk stratification and coordination with cardiology and obstetric teams are essential. Future efforts should aim to standardize protocols and improve maternal–fetal outcomes through evidence-based anesthetic planning. Full article

Toxoplasma gondii is an Apicomplexan parasite that possesses a well-developed system of scavengers of reactive oxygen species (ROS). Among its components, T. gondii mitochondrial superoxide dismutase (TgSOD2) is essential, as predicted by the CRISPR phenotype index and evidenced by the non-viability of its constitutive knockouts. As an obligate intracellular parasite, TgSOD2 is upregulated during extracellular stages. Herein, we generated a viable TgSOD2 knockdown mutant using an inducible auxin–degron system to explore the biological role of TgSOD2 in T. gondii. Depletion of TgSOD2 led to impaired parasite growth and replication, reduced mitochondrial membrane potential (MMP), abnormalities in the distribution of ATP synthase within its mitochondrial electron transport chain (mETC), and increased susceptibility to mETC inhibitors. Through a proximal biotinylation approach, we identified the interactions of TgSOD2 with complexes IV and V of its mETC, suggesting that these sites are sensitive to ROS. Our study provides the first insights into the role of TgSOD2 in maintaining its mitochondrial redox homeostasis and subsequent parasite replication fitness. Significance: Toxoplasma gondii infects nearly a third of the world population and can cause fetal miscarriages or life-threatening complications in vulnerable patients. Current therapies do not eradicate the parasite from the human hosts, rendering them at risk of recurrence during their lifetimes. T. gondii has a single mitochondrion, which is well-known for its susceptibility to oxidative damage that leads to T. gondii’s death. Therefore, targeting T. gondii mitochondrion remains an attractive therapeutic strategy for drug development. T. gondii’s mitochondrial superoxide dismutase is an antioxidant protein in the parasite mitochondrion and is essential for its survival. Understanding its biological role could reveal mitochondrial vulnerabilities in T. gondii and provide new leads for the development of effective treatments for T. gondii infections. Full article

The cryopreservation of ovarian tissues from fish has recently been carried out for several endangered and commercially valuable species. However, previous studies in this context have focused on the cryopreservation of immature ovaries—mainly through slow freezing and vitrification—which requires specialized freezing equipment or higher cryoprotectant concentrations to keep cell viability. Therefore, the aim of this study was to explore a convenient, rapid, efficient and less toxic method for the cryopreservation of ovaries at the stage of vitellogenesis from yellow drum (Nibea albiflora), an economically important marine fish. The ovaries at the stage of vitellogenesis were isolated and cut into blocks of approximately 1 cm³, then cryopreserved with 15% propylene glycol (PG), fetal bovine serum (FBS) and 0.2 M trehalose as cryoprotectants. Finally, the samples were treated using three different freezing procedures, including a −80 °C refrigerator, liquid nitrogen, and their combination. After 7 days, the tissues were thawed and digested, and the cell survival rates and gene expression levels were detected using cell viability assay kits and qRT-PCR, respectively. The results of the viability assay showed that the procedure of ovarian tissue storage at −80 °C in a refrigerator for 1 h, followed by transfer to liquid nitrogen, resulted in the highest cell survival rate (>90%). Furthermore, the germ cells at various phases were of normal size; presented a full, smooth surface and regular shape; and did not show any signs of cell rupture, atrophy, depression, granulation or cavitation. Furthermore, the qRT-PCR results revealed that genes related to reproductive development, such as vasa, foxl2, zp3 and gsdf, were all down-regulated under the optimal protocol, while the expression of the nanos2 gene (which is specifically distributed in oogonia) maintained a higher level, similar to that in the control group. This indicated that the viability of germ stem cells (oogonia) was not weakened after freezing and that oogonia could be isolated from the cryopreserved ovaries for germ cell transplantation. The present study successfully establishes an optimal cryopreservation protocol for ovarian tissues from Nibea albiflora, providing reference for the preservation of ovaries at the stage of vitellogenesis from other species. Full article

The aim of this work was to investigate the relationship between the growth rate of tumor cells and their fractionation gain. Two head and neck squamous cell carcinoma (HNSCC) cell lines, one human papillomavirus (HPV) negative (HPV−) and one HPV+, and a primary fibroblast cell line were supplemented with four different concentrations of fetal bovine serum (FBS) to achieve different division rates. The effect of five different fractionation regimens was studied, namely 1 × 10 Gy, 2 × 5 Gy, 3 × 3.3 Gy, 4 × 2.5 Gy, and 5 × 2 Gy. Survival was studied using the colony-forming assay. Different concentrations of FBS were used to achieve different doubling rates for all cell lines. The HPV+ cell line was significantly more sensitive to radiation than the HPV− cell line in all fractionation schemes. The fibroblast cell line was less sensitive at low fractionation compared to the tumor cell lines. Low fractionation had a significantly higher effect, except for 5 × 2 Gy fractionation, which had a higher effect than 4 × 2.5 Gy. The number of radiosensitive mitoses during irradiation in the fractionation scheme could not explain the higher effect of 5 × 2 Gy. There was no difference in survival with the four different concentrations of FBS in all three cell lines and different fractionations. The doubling time (DT) rates of cell lines resulting from FBS deprivation do not reflect the expected increased radiation sensitivity of rapidly dividing cells. Full article

The Yanomami Indigenous Land (YIL) is heavily impacted by illegal gold mining, leading to significant contamination by methylmercury, a neurotoxin that poses severe risks to human health. The fetal brain is particularly susceptible to the neurotoxic effects of methylmercury, which can result in mild mental retardation (MMR). The goal of this study was to estimate the burden of disease (BoD) associated with methylmercury exposure in the YIL and its economic implications. The BoD calculations followed World Health Organization (WHO) methodologies. To estimate the local BoD, hair samples were collected from women of childbearing age in the Waikás, Mucajaí, Paapiu, and Maturacá regions. For broader estimates, data from the scientific literature were used. The average hair methylmercury concentrations in these investigated regions were 6.21 µg/g, 3.86 µg/g, 3.53 µg/g, and 2.96 µg/g, respectively. The MMR incidence rate (IR) in children ranged from 2.08 to 4.47 per 1000 in these regions. The Disability-Adjusted Life Years (DALYs) per 1000 births varied from 24.8 to 53.4. In the Worst-Case Scenario, MMR-IR reached 9 per 1000, with DALYs per 1000 births rising to 109.6. The estimated economic impact of methylmercury exposure ranged from USD 716,750 to USD 3,153,700. This study is the first to quantify the MMR incidence due to mercury in the YIL, highlighting the severe threat posed by gold mining to the health and survival of the Yanomami people. Full article

Objective: The aim of our study was to evaluate maternal and perinatal outcomes in pregnant women diagnosed with cancer and treated at a single referral center in Brazil. Methods: This retrospective cohort study analyzed medical records from January 2008 to December 2020. Demographic, clinical, obstetric, and tumor-related variables were assessed. Patients were divided into two groups: Group 1 (n = 28) included women diagnosed with cancer during pregnancy or up to one year postpartum, while Group 2 (n = 11) comprised those who became pregnant during cancer investigation or treatment. Results: The most prevalent cancers were breast (G1 = 11, G2 = 3), cervical (G1 = 10, G2 = 3), and hematologic (G1 = 2, G2 = 4). Treatment modalities included surgery (n = 11), chemotherapy (n = 21), and inadvertent radiotherapy in one case. Most newborns (n = 25) were delivered at term, with one miscarriage, one fetal death, and one neonatal death reported. Thirty-two newborns were appropriate for gestational age, and thirty-seven were discharged with their mothers. Preterm delivery was indicated for obstetric reasons in 61.5% of cases. Overall survival by cancer type was 54% for breast, 70% for cervical, and 100% for hematologic cancers. The total survival rate was 70.9%. Conclusions: Cervical cancer was the second most common type in this cohort. Most deliveries occurred at term, and newborns were adequate for gestational age. Despite cancer treatment during pregnancy, most neonates were discharged alongside their mothers. Full article

In cryopreservation technology, the choice of cryoprotectant plays a crucial role in cell survival and function. Different types of cryoprotectants, each with unique protective mechanisms, mitigate cellular damage from ice crystal formation during freezing. This study investigated the effects of different types and concentrations of cryoprotectants on the cryopreservation efficacy of noble scallop Mimachlamys nobilis sperm. Six cryoprotectants were tested, including four permeable cryoprotectants (dimethyl sulfoxide (DMSO), ethylene glycerol (EG), propylene glycerol (PG), methanol (MET)) and two non-permeable cryoprotectants (trehalose (TRE), fetal bovine serum (FBS)). The results showed that permeable cryoprotectants, which penetrate the cell membrane, regulate the osmotic pressure inside and outside cells to reduce dehydration damage. Among them, 10% DMSO provided the best protection, significantly preserving sperm motility, velocity, and morphology. Non-permeable cryoprotectants, although unable to penetrate cells, stabilized the extracellular environment at higher concentrations (such as FBS). Additionally, MET and FBS exhibited enhanced protective effects with increasing concentration, indicating their potential in reducing sperm structural damage at higher concentrations. Morphological observations indicated that freezing caused varying degrees of structural damage to sperm, with flagellar integrity being crucial for motility. Overall, selecting an appropriate cryoprotectant and concentration is essential for the efficient cryopreservation of M. nobilis sperm, providing a valuable reference for conserving germplasm resources of marine species. Full article

Background/Objectives: Congenital heart disease (CHD) is the most common birth defect, an important cause of morbidity and mortality, with a reported prevalence of 5–12 per 1000 live births. The aim of our study was to identify the role of fetal morphological ultrasound examination in the first and second trimester of pregnancy in the detection of fetal congenital cardiac anomalies in a low-risk population. Methods: We performed a retrospective study in a tertiary fetal medicine center in Emergency Hospital Craiova, Romania. The longitudinal analysis combined first- and second-trimester screening using improved ultrasound protocols. Our study evaluated 8944 pregnant women with singleton pregnancies in a 6-year period between January 2018 and December 2023. All ultrasound examinations were performed using a standard extended protocol according to the main guidelines’ recommendations for the detection of fetal anomalies. Results: In the first trimester of pregnancy, 37 cases with cardiac anomalies were diagnosed. Thirteen of these cases were associated with genetic anomalies (Down syndrome—eight cases, Edwards syndrome—four cases, Turner syndrome—one case). Some of these pregnancies were associated with at least one of the minor ultrasound markers (inverted ductus venosus, abnormal flow in the tricuspid valve, presence of choroid plexus cysts, absent/hypoplastic nasal bone). In the second trimester of pregnancy, 17 cases of cardiac anomalies were diagnosed. From these cases, one was associated with genetic anomalies (DiGeorge Syndrome), and one case developed hydrops and delivered prematurely in the early third trimester. Conclusions: Ultrasound screening for the detection of congenital heart disease is feasible early in pregnancy, but some anomalies would be obvious later in pregnancy. An early diagnosis using an extended ultrasound protocol, genetic testing, and a multidisciplinary evaluation would improve the prognosis and the overall survival rate by delivering in a tertiary center that allows for rapid cardiac surgery in dedicated cases. Full article

Apoptosis is critical in placental development, and its dysregulation is linked to pregnancy complications such as intrauterine growth restriction (IUGR) and preeclampsia (PE). Environmental exposures, particularly secondhand smoke (SHS) and e-cigarettes (eCigs), may contribute to placental dysfunction through apoptotic pathways. This study examined the effects of SHS and eCig exposure on placental apoptosis and growth-regulatory proteins in a murine model. C57BL/6 pregnant mice were exposed to SHS or eCigs at two critical gestational time points: early trophoblast invasion (E12.5 to E18.5) and established invasion (E14.5 to E18.5). Placental tissues were collected and analyzed for pro-apoptotic and anti-apoptotic markers, heat shock proteins, insulin-like growth factor-binding proteins (IGFBPs), and growth regulators. SHS exposure increased pro-apoptotic markers (BAD, Fas/FasL) and decreased mitochondrial function markers (cytochrome c), indicating compromised cellular survival. Both SHS and eCig exposure reduced anti-apoptotic markers (BCL-2, HSP27, survivin) and growth regulators (IGF-1, IGFBPs). SHS and eCig exposure create a pro-apoptotic environment in the placenta, potentially impairing fetal development through altered apoptotic and growth-regulatory pathways. These findings underscore the risks of environmental exposures during pregnancy, highlighting the need for strategies to minimize maternal exposure to SHS and eCigs. Full article

Background: Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties. Objective: To determine if dietary soy interventions during pregnancy would be sufficient to normalize central nervous system structure and function, we examined the effects of maternal gestation-limited dietary soy on cerebellar postnatal development, motor function, and critical signaling pathways. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source. The ethanol and soy feedings were discontinued upon delivery. The offspring were subjected to rotarod motor function tests, and on postnatal day 35, they were sacrificed to harvest cerebella for histological and molecular studies. Results: Despite the postnatal cessation of alcohol exposure, chronic gestational exposure reduced brain weight, caused cerebellar hypoplasia, and impaired motor performance. Gestational dietary soy prevented the ethanol-associated reduction in brain weight and largely restored the histological integrity of the cerebellum but failed to normalize motor performance. Ethanol withdrawal abolished the impairments in insulin/IGF signaling that were previously associated with ongoing ethanol exposures, but ethanol’s inhibitory effects on Notch and Wnt signaling persisted. Soy significantly increased cerebellar expression of the insulin and IGF-1 receptors and abrogated several ethanol-associated impairments in Notch and Wnt signaling. Conclusions: Although gestation-restricted dietary soy has significant positive effects on neurodevelopment, optimum prevention of FASD’s long-term effects will likely require dietary soy intervention during the critical periods of postnatal development, even after alcohol exposures have ceased. Full article

Although every cell biologist knows the importance of selecting the right growth conditions and it is well known that the composition of growth medium may vary depending on a product brand or lot affecting many cellular processes, still those effects are poorly systematized. We addressed this issue by comparing the effect of 12 fetal bovine sera (FBS) and eight growth media from different brands on the morphological and functional parameters of five cell types: lung adenocarcinoma, neuroblastoma, glioblastoma, embryonic kidney, and colorectal cancer cells. Using high-throughput imaging, we compared cell proliferation; performed morphological profiling based on the imaging of 561,519 cells; measured extracellular regulated kinases (ERK1/2) activity, mitochondria potential, and lysosome accumulation; and compared cell sensitivity to drugs, response to EGF stimulation, and ability to differentiate. We found that changes in cell proliferation and morphology were independent, and morphological changes were associated with differences in mitochondria potential or the cell’s ability to differentiate. Surprisingly, the most drastic differences were detected in serum-free conditions, where medium choice affected cell survival and response to EGF. Overall, our data may be used to improve the reproducibility of experiments involving cell cultures, and the effects of 28 growth conditions on proliferation and 44 morphological parameters can be explored through a Shinyapp. Full article

Prenatal alcohol exposure (PAE) affects around 40,000 newborns every year and poses a significant health risk. Although much is already known about the neurotoxic mechanisms of PAE, new findings continue to emerge. Studies with mouse models show that PAE leads to overexpression of proinflammatory cytokines and chemokines in the brain, which disrupts important neurodevelopmental processes such as cell migration, survival and proliferation of neurons. The chemokine CXCL16 is overexpressed in the brain following various impairments, including PAE. This study shows that CXCL16 expression varies by developmental stage and sex, consistent with known sexual dimorphism in immune responses. In females, CXCL16 expression may be influenced by estrogen-related mechanisms, possibly related to the alcohol-mediated rebound effect described here. In contrast, the male hippocampus shows greater resilience to PAE-induced CXCL16 changes. Furthermore, the presence of CXCL16 in neuronal nuclei suggests a role in gene regulation, similar to other chemokines such as CCL5 and CXCL4. These findings shed light on the role of chemokines in hippocampal neuroplasticity and may pave the way for better treatment of fetal alcohol spectrum disorder (FASD). Full article

Intracranial hemorrhage is a rare yet potentially devastating event during pregnancy with a significant risk of maternal and fetal mortality and morbidity. The risk of intracranial hemorrhage increases during the third trimester of pregnancy and is greatest during labor and the postpartum period. Interdisciplinary diagnosis and treatment of the pregnant population often begins in the emergency department setting and is key to increasing patient survival rates through immediate and adequate treatment, including emergency medicine, neurosurgical and obstetrical procedures. A unique case report with a diagnostic pathway for intracranial hemorrhage due to eclampsia in a primipara at 24 weeks of gestation is presented, illustrating potential diagnostic dilemmas as the patient rapidly progresses into hemolysis, elevated liver enzymes and low platelets syndrome. A literature review was conducted to uncover the etiology of intracranial hemorrhage during pregnancy, as well as its diagnostic challenges and treatment. Pregnancy should not be viewed as a barrier to performing angiography or endovascular treatment for vascular causes of intracranial hemorrhage. Patient transport to a tertiary reference center and the interdisciplinary cooperation of specialists are key to achieving correct and rapid treatment. Continuous prevention of preeclampsia and patient education are necessary to decrease the incidence of eclampsia and its complications. Key message: Intracranial hemorrhage and eclampsia in pregnant patients are rare yet may result in high rates of maternal and fetal morbidity and mortality. The diagnostic process is difficult and requires interdisciplinary cooperation to start the correct treatment immediately. Full article

Erythropoietin (EPO) is a key regulator of erythrocyte production, promoting erythroid progenitor cell survival, division, and differentiation in the fetal liver and adult bone marrow. Mice lacking EPO or its receptor (EPOR) die in utero due to severe anemia. Beyond hematopoiesis, EPO influences non-hematopoietic tissues, including glucose and fat metabolism in adipose tissue, skeletal muscle, and the liver. EPO is used to treat anemia associated with chronic kidney disease clinically and plays a role in maintaining metabolic homeostasis and regulating fat mass. EPO enhances lipolysis while inhibiting lipogenic gene expression in white adipose tissue, brown adipose tissue, skeletal muscle, and the liver, acting through the EPO-EPOR-RUNX1 axis. The non-erythroid EPOR agonist ARA290 also improves diet-induced obesity and glucose tolerance providing evidence for EPO regulation of fat metabolism independent of EPO stimulated erythropoiesis. Therefore, in addition to the primary role of EPO to stimulate erythropoiesis, EPO contributes significantly to EPOR-dependent whole-body metabolic response. Full article