Search Results (295)

Background: Hypertensive disorders of pregnancy (HDP), particularly gestational hypertension and preeclampsia, are major causes of maternal and perinatal morbidity. Metabolic disorders such as gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), obesity, and polycystic ovary syndrome (PCOS) share mechanisms with HDP, including insulin resistance, inflammation, oxidative stress, endothelial dysfunction, and placental maladaptation. Metformin may influence these pathways, but its clinical effect on hypertensive outcomes remains uncertain. Methods: A focused narrative review was conducted using structured, targeted searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for literature published primarily from January 2015 through March 2026, supplemented by landmark studies, clinical guidelines, randomized trials, large observational cohorts, systematic reviews, meta-analyses, and mechanistic and placental studies. Evidence was selected for its relevance to the predefined phenotype-based framework and synthesized qualitatively across mechanistic, clinical, and translational domains. Results: Metformin improves insulin sensitivity and may reduce gestational weight gain, metabolic stress, inflammatory signaling, and oxidative stress. Some randomized trials and meta-analyses in GDM, obesity, and PCOS suggest lower rates of pregnancy-induced hypertension or preeclampsia, whereas recent randomized and population-based studies report neutral effects. Findings are limited by heterogeneous populations, late treatment initiation, variable comparators, supplemental insulin use, inconsistent HDP definitions, and insufficient statistical power. Conclusions: Metformin may act as a metabolic and vascular modifier in selected pregnancies, but current evidence does not support its routine use specifically for HDP prevention. Its public health value lies primarily in accessible metabolic treatment and integration into comprehensive antenatal and postpartum risk reduction pathways, rather than replacement of aspirin, blood pressure surveillance, or maternal–fetal monitoring. Full article

Chronic hyperglycemia disrupts the retinal neurovascular unit, making diabetic retinopathy (DR) the leading cause of adult vision loss. The hallmarks of DR include pathological angiogenesis, vascular leakage, and neurodegeneration. Although vascular endothelial growth factor A (VEGF-A) is a key mediator of these abnormalities and anti-VEGF therapies remain the standard treatment, many patients exhibit incomplete responses, and these therapies do not adequately address inflammation or fibrosis. Placental growth factor (PlGF), a VEGF family member that selectively binds to VEGFR1, has emerged as an important contributor to retinal neovascularization, vascular dysfunction, barrier breakdown, and microinflammation in DR. Unlike VEGF-A, PlGF modulates distinct responses among retinal neurons, glial cells, and vascular cells, with its abnormal expression closely associated with disease progression from non-proliferative to proliferative DR. This review summarizes the context-dependent functions of PlGF in the diabetic retina, compares PlGF–VEGFR1 signaling with VEGF-A–VEGFR2 pathways, and discusses preclinical and clinical evidence supporting PlGF inhibition as a potential complementary approach to existing anti-VEGF therapy. Full article

Astrocytic function imbalance is a key factor affecting cerebral ischemia rehabilitation. Mesenchymal stem cells have therapeutic potential for cerebral ischemia, but their mechanisms remain unclear. This study explored how placental mesenchymal stem cells pro-mote astrocytes towards the A2 phenotype, which benefits the repair of cerebral ischemia injury. We established the animal model of middle cerebral artery ischemia/reperfusion and an in vitro interleukin-1β-treated astrocyte inflammation model and utilized neuro-logical function assessment, 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence staining, Western blotting and other methods to evaluate the impact and associated mechanisms of transplanting placental mesenchymal stem cells into rats with cerebral ischemia–reperfusion injuries. The results demonstrated that transplantation of placental mesenchymal stem cells ameliorated neurological dysfunction and histopathological damage, alleviated neuroinflammation and enhanced neurotrophic factor levels, promoted the polarization of interleukin-1β-treated astrocytes toward the A2 phenotype, and suppressed the abundance of core mediators within the cerebral TGF β1/Smad signaling cascade in ischemia/reperfusion model. Collectively, placental mesenchymal stem cell grafting facilitates the polarization of cerebral astrocytes toward the protective A2 phenotype, presumably by regulating the TGF β1/Smad signaling cascade in ischemic brain injury. Full article

Inflammation-induced placental dysfunction is a major contributor to pregnancy complications. Activation of NF-κB and NLRP3 inflammasome pathways in the placenta is a key driver of this pathology. Decursinol, a natural coumarin derivative from Angelica gigas, possesses anti-inflammatory properties; however, its effect on placental inflammation remains unclear. Therefore, in this study, we investigated the protective effects of decursinol against lipopolysaccharide (LPS)-induced placental inflammation and trophoblast dysfunction and explored the underlying molecular mechanisms. Decursinol significantly inhibited LPS-induced NLRP3 inflammasome activation and NF-κB/p65 signaling in Sw.71 human trophoblast cells, reducing interleukin-1β secretion and pro-inflammatory gene expression. It restored the trophoblast invasive capacity and preserved mesenchymal marker expression suppressed by LPS. It also improved the fetal and placental weights, restored the placental architecture, and attenuated placental NLRP3 inflammasome activation and cytokine expression in vivo. Mechanistically, decursinol preserved the mitochondrial homeostasis, reduced mitochondrial reactive oxygen species levels, and upregulated antioxidants and mitochondrial biogenesis-related gene levels, exerting effects comparable to those of mitochondria-targeted antioxidant Mito-TEMPO. These findings suggest that decursinol protects against LPS-induced trophoblast dysfunction and adverse pregnancy outcomes by preserving mitochondrial functions and suppressing NLRP3/NF-κB-mediated inflammation. Overall, our results highlight decursinol as a promising therapeutic candidate for inflammation-associated pregnancy complications. Full article

Beginning with a general understanding of catastrophic obstetric collapse (COC), it has been established that a catastrophic obstetric collapse is typically the result of sudden massive bleeding requiring emergency peripartum hysterectomy (EPH); this is different from historical views of what constitutes a catastrophic obstetric collapse. Current studies have found evidence that a catastrophic obstetric collapse can be the result of a longer-duration process involving gradual maternal physiological destabilization, the culmination of which creates a “maternal point of no return” for the mother. As a result of disrupting the maternal–fetal interface in placenta accreta spectrum disorders (PASDs), there are many abnormalities present in the decidua, such as: defective decidualization, fragmentation of the extracellular matrix, aberrant angiogenesis, continued hypoxic signals, and the persistence of invasive trophoblastic phenotypes. These structurally fragile vascular interfaces will eventually undergo endothelial dysfunction, oscillatory shear stress, glycocalyx injury, oxidative damage and progressive depletion of the maternal vascular adaptive reserve. Chronic inflammation will also continue to amplify immune thrombosis, alter complement function, facilitate NETosis, and cause widespread instability in diffuse microvasculature, leading to a reduced ability of the maternal system to tolerate physiological stress while maintaining macrocirculatory stability. Additionally, invasive placentation may lead to mitochondrial dysfunction, decreased oxidative phosphorylation, disrupted intracellular calcium homeostasis, ferroptotic lipid peroxidation, and redox-mediated endothelial injury, leading to a progressive limitation in the mother’s bioenergetic adaptability to hemorrhage. Ultimately, these events seem to culminate in a threshold condition where endothelial disorganization exists along with capillary transit time heterogeneity, impaired oxygen diffusion, metabolic instability, and progressive desynchrony of vascular, inflammatory, coagulative and mitochondrial networks before eventual hemodynamic collapse. Therefore, based on these findings, we propose the concept of the “Maternal Point of No Return” as a transitional state in which physiological adaptations begin to fail and irreversibly destabilize at a systems level. Lastly, we review potential applications of current technological advancements, including artificial intelligence (AI), radiomic-based placental phenotyping, exosomal biology, physiological variability analysis, spatial multi-omics, and digital twin physiology, to enable future precision-obstetrics strategies to identify a decline in maternal resilience prior to irreversible decompensation. Full article

Placental inflammation and dysfunction play critical roles in adverse pregnancy outcomes, including preeclampsia and intrauterine growth restriction. Exposure to environmental factors, such as dietary toxins, infectious agents, and pollution, is thought to increase the risk of these outcomes. Despite the widespread use of HTR-8/SVneo and BeWo cells as trophoblast models, their comparative sensitivity to maternal exposome-related stimuli has not been systematically evaluated within the same experimental framework. we examined the responses of HTR-8/SVneo and BeWo trophoblast cell lines to mycotoxin deoxynivalenol (DON), an inflammatory cytokine cocktail (CC; TNF-α, IL-1β, IFN-γ), and particulate matter (PM2.5). Cells were seeded with either 0.2% or 1% penicillin/streptomycin (P/S) and exposed for 24 h. Cytokine secretion (IL-6 and IL-8), human chorionic gonadotropin (hCG) production, and mRNA and protein expression of junctional markers (ZO-1, OCLD, CLDN-3, CLDN-4, E-CAD) were analysed. DON significantly increased IL-6 secretion in both cell lines and elevated IL-8 levels in HTR-8/SVneo cells only. DON suppressed hCG production in both cell lines. CC exposure markedly elevated IL-6 and IL-8 levels, particularly in HTR-8/SVneo cells, without affecting hCG level. PM exposure did not significantly alter IL-6, IL-8, or hCG levels in either cell line. DON and CC altered the mRNA and protein expression of junctional markers in BeWo cells(ZO-1, OCLD, CLDN-3,CLDN-4), whereas HTR-8/SVneo cells showed more limited changes. Most cellular responses were consistent across both P/S concentrations. HTR-8/SVneo and BeWo cells exhibit differential sensitivity to DON, CC, and PM2.5, underscoring the importance of cell model selection in in vitro placental toxicology research. These results provide a comparative framework for interpreting trophoblast responses to maternal exposome-related stimuli and highlight the need for functional validation in future studies. Full article

The first trimester (FT) of pregnancy is characterized by rapid placental growth and differentiation, rendering this period sensitive to maternal metabolic influences. Maternal obesity is associated with chronic low-grade inflammation and altered redox homeostasis with implications in later cardiometabolic risk in offspring, yet its impact on early placental oxidative stress remains unclear. Here, we investigated whether maternal overweight and obesity are associated with oxidative lipid and protein damage and altered expression of antioxidant enzymes and stress signaling pathways. Placental tissue from lean (BMI < 25 kg/m²), overweight (BMI ≥ 25 kg/m²) and obese (BMI ≥ 30 kg/m²) non-smoking women (5–12 weeks’ gestation) was analyzed. Oxidative damage was assessed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine, and antioxidant and stress-related transcripts were quantified using targeted mRNA arrays. Explants were exposed to increased oxygen tension or TNF-α to evaluate transcriptional responsiveness. No differences in oxidative lipid or protein modifications were detected between groups. In contrast, overweight and obesity were associated with reduced expression of selected antioxidant enzymes and transcriptional remodeling of MAPK-related genes. These changes correlated with IL6 expression but not with oxidative damage markers. Collectively, maternal overweight and obesity are linked to inflammation-associated transcriptional adaptation in FT placenta without detectable oxidative injury. Full article

This systematic review assessed transcriptomic evidence on the molecular mechanisms underlying spontaneous preterm birth (sPTB). Major electronic databases were searched from inception to October 2025. Eligible studies examined RNA transcriptomic profiles from maternal pregnancy-related tissues or biofluids in spontaneous preterm labor (sPTL) or preterm prelabor rupture of membranes (PPROM), while indicated or iatrogenic preterm births were excluded. Two reviewers independently screened studies, extracted differentially expressed genes (DEGs), and assessed study quality. DEGs were summarized by tissue type, and recurrent concordant genes were analyzed using Gene Ontology, Reactome, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, with false discovery rate < 0.05 considered significant. Twenty studies were included. Transcriptomic data were derived from placental villi, maternal peripheral blood, decidua, fetal membranes, myometrium, amniotic fluid, and vaginal secretions. Placental villi findings suggested proliferative-metabolic reprogramming and impaired maternal–fetal immune–structural homeostasis, whereas maternal blood profiles reflected systemic immune–inflammatory activation and dysregulated lipid-metabolic pathways. sPTL and PPROM showed potentially distinct signatures involving extracellular matrix disruption, collagen remodeling, matrix degradation, and myeloid/neutrophil-associated inflammation. Transcriptomic profiling may support non-invasive sPTB risk assessment, but standardized, phenotype-specific longitudinal studies are needed to confirm predictive value and clinical utility. Full article

Pregnancy involves profound metabolic, hormonal, and immunological adaptations essential for fetal development; however, disturbances may lead to complications such as preeclampsia (PE), pre-gestational diabetes, and gestational diabetes mellitus (GDM). These conditions are closely linked to oxidative stress, inflammation, endothelial dysfunction, impaired placentation, and metabolic dysregulation. Consequently, dietary strategies capable of modulating these pathways are of increasing interest. Edible and medicinal mushrooms are widely studied as functional food due to the content of bioactive compounds with antioxidant, anti-inflammatory, immunomodulatory, and metabolic regulatory effects. This review summarizes the nutritional composition of mushrooms and highlights key bioactive constituents with antioxidant and metabolic regulatory properties. Among them, ergothioneine has emerged as a key molecule due to its potent redox-buffering capacity and its potential involvement in the activation of the Nrf2 signaling pathway, a master regulator of cellular antioxidant defense. Through modulation of Nrf2-dependent gene expression, mushroom-derived compounds may contribute to improved cellular resilience against oxidative damage relevant to PE and GDM pathophysiology. Mushroom consumption has additionally been associated with improved glycemic control and enhanced antioxidant defenses in experimental and limited clinical studies, although evidence regarding the prevention or management of hypertensive and metabolic pregnancy complications remains insufficient. Although preclinical findings are promising, clinical evidence remains limited. Further well-designed prospective studies and randomized controlled trials are required to determine efficacy, safety, optimal intake, and active compounds responsible for these effects. Nevertheless, current evidence supports the biological plausibility that edible and medicinal mushrooms are promising dietary modulators of the ergothioneine–Nrf2 axis with potential relevance for maternal–fetal health. Full article

Background and Clinical Significance: Superficial postoperative wound dehiscence after cesarean delivery is insufficiently described in the literature, and evidence guiding management in high-risk patients remains limited. Case Presentation: We report a case of superficial wound dehiscence in a patient who underwent cesarean delivery following a motor vehicle accident with non-reassuring fetal heart tones and placental abruption. Her medical history included Hepatitis C infection, methadone dependence, endocarditis, and a prior episode of rapid wound dehiscence after laparoscopic surgery incisions closed with absorbable suture. Conclusions: Although many studies demonstrate no significant difference in dehiscence rates across closure methods, including suture, metal staples, and absorbable staples, clinicians should recognize that underlying medical conditions associated with inflammation or a history of prior wound dehiscence may increase the risk of complications when absorbable suture or absorbable staples are used. Careful assessment of patient-specific risk factors may help guide optimal closure technique in high-risk obstetric populations. Full article

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal–fetal crosstalk, mediated largely through placental function, coordinates the transfer of metabolic, endocrine, and immune signals that are essential for normal cardiac and vascular development. Disruptions in maternal physiology—including metabolic disorders, hypertensive conditions, inflammation, and environmental stress—can perturb this communication network and alter the intrauterine milieu. These changes induce persistent modifications in cardiomyocyte growth, endothelial function, and key regulatory pathways, thereby contributing to long-term cardiovascular risk. Emerging studies highlight that cardiovascular programming is governed by interconnected mechanisms involving epigenetic regulation, mitochondrial function, immune signaling, and intercellular communication. This review synthesizes current evidence on how maternal–fetal crosstalk shapes cardiovascular development beyond genetic determinants and provides an integrated framework linking early-life exposures to lifelong cardiovascular health. Full article

L-citrulline is a non-protein amino acid with critical roles in perinatal and neonatal physiology through the intestinal–renal arginine–citrulline axis and nitric oxide (NO) production. During pregnancy, L-citrulline supports placental angiogenesis, vascular adaptation, and fetal growth through augmentation of arginine availability and endothelial NO production. In neonates, particularly preterm infants, developmental immaturity of citrulline and arginine synthesis contributes to hypoargininemia and may increase susceptibility to necrotizing enterocolitis, bronchopulmonary dysplasia with pulmonary hypertension, sepsis, and impaired intestinal function. Although L-citrulline has emerged as a promising modulator of NO bioavailability, prior reviews have largely focused on either adult cardiovascular disease or isolated neonatal applications, with limited integration of its mechanistic and translational relevance across the perinatal and neonatal continuum. Collectively, current evidence supports L-citrulline as a promising translational target in maternal–fetal and neonatal medicine because of its central role in vascular, inflammatory, and metabolic regulation. However, adequately powered clinical trials are needed to define optimal dosing, timing, patient selection, and long-term outcomes before routine clinical implementation can be recommended. This review provides a comprehensive evaluation of L-citrulline metabolism and its therapeutic potential from pregnancy through neonatal life, with emphasis on the intestinal–renal arginine–citrulline axis, endothelial function, and NO-mediated vascular regulation. We specifically examine the role of citrulline in key pathophysiologic mechanisms underlying maternal and neonatal disease, including endothelial dysfunction, impaired NO bioavailability, inflammation, oxidative stress, and abnormal placental vascular remodeling. Full article

Microplastics constitute an emerging contaminant of major concern in Latin America, where human exposure predominantly occurs through ingestion of drinking water and marine/estuarine food chains. This review synthesises available evidence on occurrence, exposure pathways, toxicological mechanisms, and regional public health risks, while examining regulatory and monitoring limitations that constrain effective risk management. Reported concentrations in drinking water show a wide range (1–1194 particles/L), dominated by PET, PP, and PS, with fibres and fragments as the main morphotypes. In commercial marine species, prevalence reaches 70–100%, with burdens up to 44 particles/g in oysters and ~90 particles/250 g in mussels. Estimated Daily Intake is 2–5 times higher in children (e.g., Chile: 13.03 vs. 5.59 particles/day in adults). Toxicological mechanisms include oxidative stress, chronic inflammation (NF-κB pathway), endocrine disruption, intestinal dysbiosis, systemic translocation, and placental transfer, exacerbated by vectorization of local co-contaminants (Hg from mining, Cd/Pb from agriculture). Risk indices indicate extreme danger in Brazil, Chile, and Ecuador, where data are available. Significant geographic and methodological gaps persist, with Brazil dominating research (~50–60%). Multicenter biomonitoring, harmonised surveillance networks, and SDG-aligned policies are urgently needed to reduce exposure burdens, protect vulnerable populations, and advance toward comprehensive regional risk assessment. Full article

Placental examination is frequently performed following adverse fetal or neonatal neurologic outcomes to elucidate the cause or timing of injury. In practice, however, the placenta more often serves as a biologic archive of fetal stress, adaptation, and reduced physiologic reserve rather than a definitive record of injury. This review synthesizes current research linking placental pathology to perinatal brain injury, with emphasis on biological mechanisms and temporal interpretation. We examine how placental findings inform assessments of intrauterine stress, impaired placental or fetal perfusion, inflammation, and diminished placental reserve. Surrogate markers of fetal stress, including nucleated red blood cells and intrauterine meconium passage, provide contextual evidence regarding the duration and severity of intrauterine compromise but do not establish causality. Finally, we review acute circulatory disruption, chronic or intermittent impairment of fetal blood flow, umbilical cord-related pathology, and immune-mediated placental disorders that increase vulnerability to neurologic injury. Full article

Placenta-derived extracellular vesicles (EVs), particularly exosomes, serve as key mediators that influence metabolic programming in offspring under adverse early nutritional conditions, such as maternal obesity or gestational diabetes. They respond to maternal nutritional disturbances—such as obesity or gestational diabetes—by altering the composition of the miRNAs and proteins they carry. Evidence from in vivo and in vitro studies suggests that these modified EVs influence offspring metabolic programming through multiple putative pathways: regulating fetal pancreatic β-cell development and function, modulating lipogenesis via PPARγ signaling, affecting placental angiogenesis, and promoting inflammation and epigenetic alterations. By transmitting maternal environmental signals to the fetus, placental EVs are hypothesized to contribute to long-term metabolic phenotypes and disease susceptibility. This review critically examines the current evidence positioning placental EVs as key messengers in maternal–fetal communication, evaluates the strength of evidence supporting their role in shaping offspring metabolic health, identifies major knowledge gaps (e.g., limited direct evidence in human offspring, lack of standardized isolation methods), and suggests their potential as early intervention biomarkers or therapeutic targets for preventing metabolic disorders in offspring. We also highlight the need for prospective cohort studies and mechanistic validation in appropriate animal models to establish causality. Full article