Search Results (419)

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period. Full article

Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection strategy employing a target-triggered hybridization chain reaction (HCR) to amplify signals and in situ photocleavable mass tags (PMTs) for the simultaneous detection of multiple targets. Hairpin DNAs modified with PMTs and immobilized loop structures on magnetic particles (Loop@MPs) were engineered for each target, and their hybridization and amplification efficiency was validated using native polyacrylamide gel electrophoresis (PAGE) and laser desorption/ionization MS (LDI-MS), with silica@gold core–shell hybrid (SiAu) nanoparticles being employed as an internal standard to ensure quantitative reliability. The system exhibited excellent sensitivity, with a detection limit of 415.12 amol for the hepatitis B virus (HBV) target and a dynamic range spanning from 1 fmol to 100 pmol. Quantitative analysis in fetal bovine serum confirmed high accuracy and precision, even under low-abundance conditions. Moreover, the system successfully and simultaneously detected multiple targets, i.e., HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), mixed in various ratios, demonstrating clear PMT signals for each. These findings establish our approach as a robust and reliable platform for ultrasensitive multiplexed detection, with strong potential for clinical and biomedical research. Full article

Human adipose-derived stem cells (hASCs) are widely used in regenerative medicine due to their accessibility and high proliferative capacity. Platelet lysate (PL) has recently emerged as a promising alternative to fetal bovine serum (FBS), offering superior cell expansion potential; however, the molecular basis for its efficacy remains insufficiently elucidated. In this study, we performed RNA sequencing to compare hASCs cultured with PL or FBS, revealing a significant upregulation of genes related to stress response and cell proliferation under PL conditions. These findings were validated by RT–qPCR and supported by functional assays demonstrating enhanced cellular resilience to oxidative and genotoxic stress, reduced doxorubicin-induced senescence, and improved antiapoptotic properties. In a murine wound model, PL-treated wounds showed accelerated healing, characterized by thicker dermis-like tissue formation and increased angiogenesis. Immunohistochemical analysis further revealed elevated expression of chk1, a DNA damage response kinase encoded by CHEK1, which plays a central role in maintaining genomic integrity during stress-induced repair. Collectively, these results highlight PL not only as a viable substitute for FBS in hASC expansion but also as a bioactive supplement that enhances regenerative efficacy by promoting proliferation, stress resistance, and antiaging functions. Full article

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

Maternal obesity programs the fetus for increased risk of chronic disease development in early life and adulthood. We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNFα, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1α, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases. Full article

Background: Folic acid is essential for DNA synthesis and fetal development, with deficiency linked to anemia, cardiovascular disease and pregnancy complications. The clinical guidelines for women of reproductive age mandate supplementation as a universal preventive treatment regardless of blood folic acid levels; therefore, routine folic acid level testing is not recommended for this population. However, the vast majority of pregnant women do not implement the recommended preventive actions, indicating that new strategies are needed to improve that situation. Objectives: This study examined the impact of modifying the laboratory test-ordering interface in the medical record system, designed to simplify the ordering of folic acid level tests, on testing rates, deficiency detection and supplement consumption among women of reproductive age. Methods: This retrospective cohort analysis compared outcomes reflecting the impact of the modification on 43,952 women aged 18–42 years, assessed over one year pre- and post-integration. Statistical analyses included Chi-squared tests and logistic regression, with adjustments for age and socio-geographic status. Results: Post-intervention, testing rates increased from 14.74% to 17.35% (p < 0.0001), and deficiency detection rose from 6.30% to 7.38% (p < 0.0001). Supplement consumption tripled from 5.45% to 15.98% (p < 0.0001), with 91.37% of post-intervention consumers being new users. Conclusions: Modifying the presentation of tests in the laboratory test-ordering interface within electronic medical records significantly improved testing rates, enhanced deficiency detection and had a meaningful impact on treatment outcomes. These findings underscore the potential of system-level digital interventions to advance preventive care and overall health. Future research should focus on examining scalability, implementation and long-term outcomes across diverse healthcare settings. Full article

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case–control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. A total of 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59–0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68–0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63–0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71–0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82–1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal. Full article

The domestic cat is the primary reservoir host of three flea-borne Bartonella species, one of which (Bartonella henselae) causes reduced fertility and reproductive failure in experimentally infected cats. Vertical transmission of Bartonella has been documented only in B-cell deficient mice, but not immunocompetent animals. As many free-roaming cats are chronically infected with Bartonella and may be immunocompromised by environmental stress or coinfection, we attempted to isolate Bartonella from the fetal and placental tissues of pregnant queens spayed during trap–neuter–release. Four samples from each tissue (ovary, uterus, fetus, and placenta) were split for direct DNA extraction, liquid culture, and culture on a blood agar plate. Samples from infected queens were inoculated into liquid media and sampled weekly for three weeks for DNA extraction and plating. Bartonella DNA was sequenced directly from 28% (5/18) of the free-roaming queens. For these five queens, liquid enrichment culture was attempted in duplicate for fetal and placental samples. Bartonella clarridgeiae DNA was amplified using qPCR liquid enrichment cultures from the placentas of two cats. These findings suggest that viable Bartonella organisms are present in feline reproductive tissue. Additional studies are needed to assess the transplacental transmission of Bartonella spp. and Bartonella’s influence on fetal development. Full article

The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, early onset preeclampsia, and fetal growth restriction. Characterization of the normal differentiation processes is, thus, essential for the analysis of these pathologies. Our gene expression analysis, employing purified human CTB and EVT cells, demonstrates a mechanism similar to the epithelial–mesenchymal transition (EMT), which underlies CTB–EVT differentiation. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. A small subgroup of genes undergoes gains of methylation (GOM), associated with differential gene expression (DE). Prominent in this GOM-DE group are genes involved in epithelial–mesenchymal plasticity (EMP). An exemplar is the transcription factor RUNX1, for which we demonstrate a functional role in regulating the migratory and invasive capacities of trophoblast cells. This analysis highlights epigenetically regulated genes acting to underpin the epithelial–mesenchymal plasticity characteristic of human trophoblast differentiation. Identification of these elements provides important information for the obstetric disorders in which these processes are dysregulated. Full article

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus’s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood. Full article

In utero exposure to per- and polyfluoroalkyl substances (PFAS) presents significant health concerns, primarily through their role in inducing epigenetic modifications that have lasting consequences. This review aims to elucidate the impact of prenatal PFAS exposure on epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation, focusing on developmental and long-term health outcomes. The review synthesizes findings from various studies that link PFAS exposure to alterations in DNA methylation in fetal tissues, such as changes in the methylation of genes like IGF2 and MEST, which are linked to disruptions in growth, neurodevelopment, immune function, and metabolic regulation, potentially increasing the risk of diseases such as diabetes and obesity. We also highlight the compound-specific effects of different PFAS, such as PFOS and PFOA, each showing unique impacts on epigenetic profiles, suggesting varied health risks. Special attention is given to hormonal disruption, oxidative stress, and changes in histone-modifying enzymes such as histone acetyltransferases (HATs) and deacetylases (HDACs), which are pathways through which PFAS influence fetal development. Additionally, we discuss PFAS-induced epigenetic changes in placental tissues, which can alter fetal nutrient supply and hormone regulation. Despite accumulating evidence, significant knowledge gaps remain, particularly regarding the persistence of these changes across the lifespan and potential sex-specific susceptibilities. We explore how advancements in epigenome-wide association studies could bridge these gaps, providing a robust framework for linking prenatal environmental exposures to lifetime health outcomes. Future research directions and regulatory strategies are also discussed, emphasizing the need for intervention to protect vulnerable populations from these environmental pollutants. Full article

Maternal overnutrition and targeted supplements during pregnancy strongly affect fetal development in beef cattle, influencing gene expression, tissue development, and productivity after birth. As modern feeding practices often result in cows receiving energy and protein above requirements, understanding the balance between adequate nutrition and overconditioning is critical for sustainable beef production. This review synthesizes findings from recent studies on maternal overnutrition and supplementation, focusing on macronutrients (energy, protein, methionine) and key micronutrients (e.g., selenium, zinc). It evaluates the timing and impact of supplementation during different gestational stages, with emphasis on fetal muscle and adipose tissue development, immune function, and metabolic programming. The role of epigenetic mechanisms, such as DNA methylation and non-coding RNAs, is also discussed in relation to maternal dietary inputs. Mid-gestation supplementation promotes muscle growth by activating muscle-specific genes, whereas late-gestation diets enhance marbling and carcass traits. However, maternal overnutrition may impair mitochondrial efficiency, encourage fat deposition over muscle, and promote collagen synthesis, reducing meat tenderness. Recent evidence highlights sex-specific fetal programming differences, the significant impact of maternal diets on offspring gut microbiomes, and breed-specific nutritional responses, and multi-OMICs integration reveals metabolic reprogramming mechanisms. Targeted trace mineral and methionine supplementation enhance antioxidant capacity, immune function, and reproductive performance. Precision feeding strategies aligned with gestational requirements improve feed efficiency and minimize overfeeding risks. Early interventions, including protein and vitamin supplementation, optimize placental function and fetal development, supporting stronger postnatal growth, immunity, and fertility. Balancing nutritional adequacy without excessive feeding supports animal welfare, profitability, and sustainability in beef cattle systems. Full article

Background/Objective: Early pregnancy loss is often caused by chromosomal abnormalities, necessitating accurate diagnostic tools. While product of conception (POC) chromosomal testing is commonly used, it can be limited by culture failure or an inability to obtain fetal tissue due to spontaneous expulsion. Cell-free fetal DNA (cff DNA) analysis provides a non-invasive alternative; however, its effectiveness in early pregnancy loss, particularly in cases where fetal components are still minimal, has not been fully established. The objective of this study was to evaluate the accuracy of pre- and postoperative cff DNA analysis for detecting fetal aneuploidy by comparing the results to those of POC chromosomal testing. Methods: In this single-center prospective cohort study, 50 women undergoing manual vacuum aspiration for pregnancy loss before 12 weeks of gestation were enrolled (February 2022–December 2024). Cff DNA analysis was performed on maternal blood samples collected pre- and postoperatively. The primary outcome was concordance between the cff DNA and POC results. Sensitivity, specificity, and factors affecting concordance were also assessed. Results: Eight participants were excluded due to unsuccessful POC culture (n = 3), suspected maternal tissue contamination in the POC sample (n = 1), mosaicism (n = 3), or triploidy (n = 1), resulting in 42 evaluable cases. Preoperative cff DNA analysis showed 88.1% concordance with POC (sensitivity 86.4% and specificity 90.0%). Postoperative analysis showed 78.6% concordance (sensitivity 72.7% and specificity 85.0%). Conclusions: The Cff DNA analysis of preoperative and postoperative maternal blood samples showed generally good concordance with conventional POC chromosomal testing in detecting fetal aneuploidy in early pregnancy loss. Full article

Background: Mitochondria are essential for placental function as they regulate energy metabolism, oxidative balance, and apoptotic signaling. Increasing evidence suggests that placental mitochondrial dysfunction may play a role in the development of many poor perinatal outcomes, including preeclampsia, intrauterine growth restriction (IUGR), premature birth, and stillbirth. Nonetheless, no systematic review has thoroughly investigated this connection across human research. This study aims to consolidate evidence from human research concerning the link between placental mitochondrial dysfunction and negative birth outcomes. Methods: A systematic search of PubMed, Scopus, and Web of Science identified human research examining placental mitochondrial features (e.g., mtDNA copy number, ATP production, oxidative stress indicators) in connection with adverse pregnancy outcomes. Methodological variety resulted in narrative data extraction and synthesis. Results: Twenty-nine studies met the inclusion criteria. Mitochondrial dysfunction was consistently associated with PE, IUGR, FGR, and PTB. The most often observed outcomes included diminished mtDNA copy number, decreased ATP production, elevated reactive oxygen species (ROS), and disrupted mitochondrial dynamics, characterized by increased DRP1 and decreased MFN2. Early-onset preeclampsia and symmetric fetal growth restriction exhibited particularly severe mitochondrial abnormalities, indicating a primary placental origin of the condition. Conclusions: A significant factor contributing to adverse pregnancy outcomes is the dysfunction of placental mitochondria. The analogous molecular signatures across many disorders suggest promising avenues for developing targeted therapies aimed at improving maternal–fetal health and predictive biomarkers. Full article