Search Results (480)

Gestational Diabetes Mellitus (GDM) increases the long-term risk for metabolic and cardiovascular diseases in the offspring. However, the underlying mechanisms are not well understood. This study investigates the impact of GDM on fetoplacental vascular function and molecular mechanisms underlying endothelial dysfunction. Clinical data and tissue samples were collected from normoglycemic (NG, n = 33) and GDM (n = 19) pregnancies. Offspring in the GDM group were delivered earlier, had a larger placental size, and had a reduced placental efficiency. Functional analysis using a Mulvany myograph demonstrated a significant impairment of insulin-mediated vasodilation in fetoplacental vessels of GDM patients compared to NG controls. This vascular dysfunction was associated with a reduction in total insulin receptor protein expression. Further investigation revealed an impaired PI3K/AKT/eNOS signaling pathway, as endothelial cells from GDM pregnancies showed a deficient insulin-induced phosphorylation of AKT. These results indicate that maternal GDM induces insulin resistance and endothelial dysfunction in the fetoplacental vasculature through impairment of the AKT/eNOS pathway, providing a key mechanism for its adverse neonatal outcomes and the increased lifelong cardiovascular risk in the offspring. Full article

The prevalence of maternal obesity is rapidly increasing, which represents a major public health concern worldwide. Currently more than 50% of all adult women are overweight or obese, and this trend is reflected in women of child-bearing age. Maternal obesity is characterized by metabolic dysfunction and chronic inflammation, and is associated with health problems in both the mother and the offspring. Intrauterine programming occurs during embryonic and fetal development, a critical period not only for the formation of tissues and organs but also for the etiology of diseases later in life. The principal mechanisms underlying fetal programming in the offspring of obese mothers appear to involve DNA methylation and chromatin remodeling within progenitor cells. Aberrant DNA methylation patterns have been identified in genes involved in insulin signaling, lipid metabolism, and appetite regulation in the placenta and fetal tissues. Histone modifications, such as acetylation and methylation of histone tails, may also play a crucial role in modulating chromatin structure and accessibility of transcriptional machinery to DNA. The persistence of such modifications throughout life, and potentially across generations, can lead to permanent alterations in gene expression, thereby contributing to the intergenerational transmission of metabolic disorders. The aim of this paper is to present an overview of the current knowledge regarding the effects of maternal obesity on fetal development and the occurrence of fetal complications, as well as long-term complications observed in adulthood related to intrauterine exposure to maternal obesity, including hypertension and cardiovascular diseases, impaired insulin secretion and resistance, diabetes mellitus, and metabolic syndrome. The mechanisms underlying fetal programming are also discussed. Full article

The Paraoxonase (PON) gene family consists of three paralogues (PON1, PON2 and PON3) that are tandemly located on chromosome 7. In this review paper, the structure and function of the encoded proteins is summarized. In addition, an overview is given on the generated animal models. Finally, their involvement in the pathogenesis of different diseases is discussed, starting from an extended screening of the literature using PUBMED and Web of Science. PON1 and PON3 are mainly expressed in the liver and released into the bloodstream, bound to high-density lipoprotein. PON2 is expressed in various tissues, including the liver, lungs, heart, placenta and testes, but remains intracellular. The name of the enzyme family reflects PON1′s ability to neutralize paraoxon, but they also exhibit lactonase and esterase activities. All three PON enzymes play a role in reducing lipid peroxides in High-Density Lipoproteïne (HDL) and low-density lipoprotein(LDL), giving them antioxidant properties. This links them to Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), a metabolic liver condition marked by the excessive accumulation of triglycerides (TG) in liver cells. In addition to their association with MASLD, the PON genes are, due to their antioxidant properties, also associated with other conditions including cardiovascular diseases, chronic kidney disease, neurological and immunological conditions up to some forms of cancer. In the latter, the antioxidant properties can result in tumor progression by protecting malignant cells from oxidative damage thus supporting survival, proliferation and metastasis indicating them as potential drug targets for treatment of cancer. Therefore, further research on this protein family can provide novel insights into their function and their potential therapeutic applicability. Full article

Post-translational modifications (phosphorylation and glutathionylation) not only assure protein diversity but are also responsible for the controlling of the biological activity of selected proteins in health and disease. The aim of the study was to monitor the profile of changes in molecular weight of proteins undergoing selected post-translational modifications by measurement of the intensity of phosphorylation and glutathionylation within the pregnancy course and parturition in cows with and without the retention of foetal membranes. The intensity of selected post-translational modifications was measured in bovine placental tissues collected during pregnancy (2nd, 4th, 5th, and 7th month, n = 4 per month) and parturition (not-retained foetal membranes (NRFM, n = 6) and retained foetal membranes (RFM, n = 6). Placental tissues were homogenised and used for the Phosphoprotein Phosphate Estimation Assay Kit and Western blotting analyses with adequate antibodies. The content of phosphorylated proteins was significantly higher (p < 0.05) in the 2nd month as compared to other months, both in the maternal and foetal parts of the placenta. Moreover, no significant differences were observed between NRFM and RFM samples. The results of Western blotting showed the shift in molecular weight and indirect content of phosphorylated selected amino acids. Further research on the role of post-translational modifications in pregnancy and parturition may give new insight into their biochemical regulation. Full article

Background/Objectives: Histological chorioamnionitis (HCAM) is a risk factor of chronic lung disease (CLD) in preterm neonates. Funisitis, an indicator of fetal inflammatory response, has been linked to adverse neonatal outcomes, but its impact on respiratory outcomes in extremely preterm neonates remains uncertain. In this study, we investigated whether HCAM with funisitis is associated with poorer respiratory outcomes when compared with HCAM alone in preterm (gestational age 22–36 weeks) neonates. Methods: This was a retrospective cohort study. We divided very low-birth weight (VLBW) preterm neonates with placenta histopathology examinations into three groups—normal, isolated HCAM, and HCAM with funisitis. Perinatal characteristics, radiographic findings, morbidities, and respiratory outcomes were compared. Results: Among 244 VLBW neonates, 25 (10.2%) had HCAM with funisitis, 88 (36.1%) had isolated HCAM, and the remaining 131 were in the normal group. Neonates with HCAM and funisitis had a significantly lower gestational age (26.44 ± 2.1 weeks) but a higher incidence of clinical chorioamnionitis (40.0%) than those with isolated HCAM (12.5%) or normal placentas (6.9%). Moreover, the incidence of cystic–interstitial lung changes before 2 weeks of postnatal age was higher in the HCAM with funisitis group (56.5%) than in the isolated HCAM group (25.0%), and the normal group (4.4%). CLD occurred in 66.7%, 37.7%, and 1.3% of these groups, respectively, and the need for home oxygen at follow-up was 26.1%, 13.7%, and 6.4%. Both isolated HCAM and HCAM with funisitis protected against severe respiratory distress syndrome. However, extremely preterm birth and funisitis had a more adverse impact on CLD development than HCAM alone (adjusted odds ratio 15.259 vs. 3.841). Conclusions: Funisitis independently predicts poor respiratory outcomes in extremely preterm infants. The long-term clinical impacts of funisitis in preterm infants should be further investigated. Full article

Background/Objectives: Myomectomy is the preferred treatment for women with uterine fibroids who desire to preserve their fertility. This study aimed to compare perinatal outcomes between Mexican women with and without a history of myomectomy, matched in a 1:2 ratio based on maternal age and parity. Methods: A retrospective cohort study was conducted involving women with and without a history of myomectomy who received prenatal care and delivered at a tertiary care hospital in Mexico City. Women with comorbidities such as pregestational diabetes, chronic hypertension, autoimmune diseases, nephropathy, cardiomyopathy, and cancer were excluded from the study. Group 1 consisted of women with a history of myomectomy, and Group 2 included matched women without such a history. The following perinatal outcomes were evaluated: miscarriage, preterm birth, cesarean section, obstetric hemorrhage, placenta previa, surgical adhesions, and obstetric hysterectomy. Adjusted relative risk (aRR) with 95% confidence intervals (CI) was calculated. Results: A total of 122 women were analyzed in group 1, and 244 in group 2. The risk of obstetric hemorrhage aRR 7.5 (95% CI 3.9–11.9), surgical adhesions aRR 11.8 (5.3–20.7), and placenta accreta aRR 15.3 (1.3–111) were significantly higher in Group 1 compared to Group 2. Other outcomes, including miscarriage, preterm birth, cesarean section, placenta previa, and obstetric hysterectomy, were similar between groups. Conclusions: Mexican pregnant women with a history of myomectomy have a higher risk of obstetric hemorrhage, surgical adhesions, and placenta accreta compared to those without such a history. Full article

Micro- and nanoplastics (MNPs) are emerging environmental immunotoxins with widespread human exposure through ingestion, inhalation, and dermal contact. Detected in the placenta, lungs, blood, bone marrow, and brain, MNPs accumulate in immune organs where they disrupt innate and adaptive cell functions. This review aims to provide a comprehensive summary of the current knowledge on how MNPs affect the immune system at the cellular and molecular levels. Experimental evidence shows that MNPs impair macrophage phagocytosis, skew dendritic cell maturation, trigger neutrophil extracellular traps, and alter T and B cell responses. Mechanistically, these effects are driven by oxidative stress, mitochondrial dysfunction, and activation of key inflammatory signaling pathways, including NF-κB, MAPK, and NLRP3 inflammasome, leading to apoptosis, pyroptosis, and chronic low-grade inflammation. Furthermore, MNP-induced disruption of epithelial barriers and gut microbiota composition undermines immune tolerance and contributes to the pathogenesis of autoimmune conditions. Preclinical models provide evidence linking MNP exposure to exacerbation of diseases such as systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis. However, human epidemiological data remain limited, highlighting the urgent need for standardized exposure protocols, advanced omics technologies, and longitudinal cohort studies are urgently needed to establish causal links and inform public health strategies. Full article

Background: Preeclampsia is a complex hypertensive disorder of pregnancy associated with significant maternal and foetal morbidity and mortality. Its pathogenesis involves placental hypoxia, oxidative stress, and impaired trophoblast invasion. Recent evidence highlights the role of microRNAs, particularly microRNA-210 (miR-210), in the molecular disruptions underlying preeclampsia. Aim: This study aims to explore the pathogenic, diagnostic, and therapeutic significance of miR-210 in preeclampsia, with emphasis on its molecular mechanisms, biomarker potential, and prospects as a therapeutic target. Methods: A systematic narrative review was conducted following PRISMA guidelines. A total of 498,184 articles were identified through eight scientific databases, and, after duplicate removal and eligibility screening, 111 peer-reviewed studies published between 2015 and 2025 were included in the final analysis. The selected literature focused on miR-210’s expression in placental tissue and maternal circulation, its molecular targets, and its clinical relevance. Results: miR-210 is consistently upregulated in preeclamptic placentas and maternal plasma. It contributes to shallow trophoblast invasion, impaired angiogenesis, mitochondrial dysfunction, and the activation of a hypoxia-induced HIF-1α feedback loop. These mechanisms are central to the disease’s pathophysiology. Clinically, miR-210 demonstrates high stability in circulation and early detectability, making it a promising diagnostic and prognostic biomarker. Experimental models have also demonstrated the therapeutic potential of miR-210 inhibition using antisense oligonucleotides or HIF-1α modulators. Conclusions: miR-210 is both a marker and mediator of preeclampsia. Its integration into diagnostic protocols and therapeutic strategies, alongside clinical validation and standardisation, may enhance early detection and personalised care in high-risk pregnancies. Full article

Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H₂O₂) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H₂O₂ treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H₂O₂ treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H₂O₂-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress. Full article

Transcription factor EB (TFEB) is expressed at high levels in the trophoblast cells of the placenta, where it plays a critical role in regulating normal vascularization. Preeclampsia (PE) is a severe complication of pregnancy with a high incidence of maternal and fetal morbidity and mortality. Gestational diabetes (GD) is a metabolic disease that can affect placental villous maturation and villous vascularity. We analyzed the expression of three different antibodies: TFEB from Invitrogen (TFEB-INV), which detects endogenous levels of TFEB only when phosphorylated at Ser211; TFEB from Bethyl Labs (TFEB-B), which recognizes and binds E-box sequences; and TFEB from Santa Cruz (C-6) (TFEB-SC), which is specifically used for epitope mapping between 440 and 470. We evaluated the presence/absence of TFEB in six placental districts: syncytiotrophoblast (STB), cytotrophoblast (CTB), extravillous trophoblast (EVT), syncytial knots, stem villi vessels, and villous capillaries. TFEB-B was significantly expressed in the stem villi vessels, STB, and villi vessels of GD cases. The lack of TFEB expression in late-onset PE appears to corroborate the role of TFEB in vascular remodeling during placental development. The positive results in STB and vessels in GD cases, regardless of the histological diagnosis, may suggest that the expression of TFEB mitigates hypoxic injury via the Akt/mTOR pathway. Full article

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for degenerative diseases due to their ability to modulate disease progression through paracrine mechanisms. Among various MSC sources, placenta-derived MSCs (PD-MSCs) offer significant advantages, including high proliferation capacity, reduced senescence, and low immunogenicity, making them ideal for allogeneic applications. In this study, we investigated the therapeutic effects of PD-MSC transplantation in an estrogen-deficiency-induced osteoporosis mouse model. Mice were divided into three groups: a normal control group, a non-transplanted osteoporosis group, and a PD-MSC-transplanted group. Our findings demonstrated that PD-MSC transplantation significantly improved osteoporosis-related parameters, including increased femur weight, bone volume, bone mineral density, and calcium deposition. Additionally, estrogen levels were elevated, bone formation markers were upregulated, and bone resorption markers were downregulated. PD-MSCs also reduced inflammatory cytokine levels while enhancing anti-inflammatory factors. Notably, the BMP/SMAD signaling pathway, crucial for bone formation, was significantly upregulated. These results suggest that PD-MSC transplantation effectively restores bone homeostasis by inhibiting osteoclast activity, promoting osteogenesis, and modulating inflammation. This study provides strong evidence supporting the potential of PD-MSCs as a novel therapeutic strategy for osteoporosis, offering a regenerative and anti-inflammatory approach to bone disease management. Full article

In Africa, the folkloric practices involving plant-based remedies play a crucial role in livestock farming, often attributed to the limited access to modern veterinary services. The use of Acacia species (including those reclassified as Vachellia species) in ethnoveterinary medicine has garnered increasing interest due to their high protein content and medicinal (including anti-parasitic) properties, offering a sustainable source of fodder particularly in arid and semi-arid regions. However, scientific assessment of their efficacy and safety remains limited. This systematic review examines the ethnoveterinary uses, biological efficacy and safety of Acacia species across Africa. A literature search was conducted using PubMed, Google Scholar and Scopus, yielding 519 relevant studies published between 2001 and 2024. After applying the inclusion and exclusion criteria, 43 eligible studies were analyzed based on their relevance, geographical location and livestock disease applications. Plants of the World online database was used to validate the names of the species and authority. Ethiopia had the highest usage of Acacia species (25%), then Nigeria (20%) followed by both South Africa (15%) and Namibia (15%). Vachellia nilotica (Acacia nilotica) was the most frequently cited species (26.3%), followed by Vachellia karroo (Acacia karroo) (15.8%). Ethnobotanical records indicate that the different Acacia species have been traditionally used to treat conditions such as diarrhea, wound infections and complications such as retained placenta. Pharmacological studies corroborate the therapeutic benefits of Acacia species with evidence of their antimicrobial, anti-inflammatory, antioxidant and anthelmintic effects, though some toxicity concerns exist at high dosages. The systematic review revealed the efficacy and safety (to some extent) of Acacia species in livestock disease management, emphasizing their potential integration into veterinary medicine. However, the dearth of in vivo studies underscores the need for pre-clinical and clinical trials to establish safe and effective dosages for use in livestock. Full article

Background/Objectives: Adenomyosis is increasingly being identified in women of childbearing age as a cause of infertility and adverse pregnancy outcomes. As hysterectomies are not suitable for fertile women, conservative surgical management has become a promising solution. We aimed to synthesize current evidence on conservative uterus-sparing surgical techniques for adenomyosis, focusing on implications for infertility treatment and pregnancy outcomes. Methods: A search of PubMed, Google Scholar, and Europe PMC from 2022 to July 2025 was conducted using combinations of the words “adenomyosis,” “fertility,” “infertility,” “pregnancy outcomes,” “adenomyomectomy,” and “uterine-sparing surgery.” Sixteen high-relevance studies were chosen that included reproductive-aged women who had conservative surgery for adenomyosis. Results: Excisional techniques such as adenomyomectomy yield pregnancy rates of >50% and live birth rates of up to 70% in focal disease, with less success in diffuse disease. Non-excisional approaches—high-intensity focused ultrasound (HIFU), radiofrequency ablation (RFA), and uterine artery embolization (UAE)—yield equivalent pregnancy (40–53%) and live birth (35–74%) rates in selected patients, with fewer surgical complications. Adjunctive hormonal therapy, particularly GnRH agonists, appears to improve outcomes. Risks include placenta accreta spectrum disorders and uterine rupture (≤6%), especially in diffuse adenomyosis. The type of lesion, location, and junctional zone thickness are strong predictors of fertility outcomes. Conclusions: Conservative surgery can augment fertility in appropriately chosen women with adenomyosis, with removal being the preferred treatment for focal disease and non-removal techniques offering encouraging alternatives in mild or intracorporeal disease. The addition of adjunct hormonal therapy and standardized patient selection criteria will optimize results. The lack of European professional society guidelines underscores the need for harmonized protocols in order to standardize the diagnosis, surgery, and reporting of results. Full article

Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic pathways that converge across these disorders. Integrating morphological evidence with mechanistic data highlights how villous maldevelopment, shallow trophoblast invasion, and aberrant vascular remodeling translate into clinical disease. Advances in biomarker research have already transformed clinical care: the sFlt-1/PlGF ratio is now established in the prediction and management of preeclampsia, while placental proteins such as PAPP-A and PP13, nucleic acid signatures including cfDNA, cfRNA and miRNAs, and extracellular vesicle cargo show promising potential for early, non-invasive detection of placental pathology. Multi-omics approaches, particularly single-cell and spatial transcriptomics combined with proteomic and metabolomic profiling, are paving the way for composite diagnostic panels that capture the polygenic and multicellular nature of placental disease. This review synthesizes current knowledge of molecular mechanisms, histological correlates, and translational biomarkers, and outlines how precision obstetrics may emerge from bridging mechanistic discoveries with clinical applications. Full article

Background/Objectives: Fetuin-A is a multifunctional glycoprotein involved in metabolic and inflammatory regulation. Although its role in insulin resistance, type 2 diabetes, and cardiovascular disease is well recognized, its relationship with pregnancy-related body mass changes remains unclear. This study aimed to explore associations between maternal BMI dynamics during and shortly after pregnancy and serum fetuin-A concentrations. Methods: Fifty-five healthy Caucasian women with term singleton pregnancies were enrolled. BMI was recorded at three time points: pre-pregnancy, before delivery, and 48 h postpartum. Based on ΔBMI (postpartum minus pre-pregnancy BMI), participants were divided into two groups: ΔBMI ≤ 1 kg/m² (n = 32) and ΔBMI > 1 kg/m² (n = 23). Serum fetuin-A levels were measured before delivery and postpartum using ELISA. Additional laboratory parameters and body composition were assessed postpartum via standard tests and bioelectrical impedance analysis (BIA). Results: No significant differences were found between groups in BMI at any single time point or in laboratory or BIA-derived parameters. However, all three BMI change indices (ΔBMI_gestational, ΔBMI_puerperal, and ΔBMI) differed significantly between groups. Fetuin-A concentrations did not differ significantly between groups. Importantly, fetuin-A levels decreased significantly after delivery in both groups, suggesting a potential role of the placenta in its regulation. A significant correlation was observed between pre-delivery fetuin-A and postpartum uric acid in Group ΔBMI > 1 kg/m² (p = 0.016), indicating a possible link in women with greater gestational weight gain. Conclusions: While fetuin-A was not directly associated with BMI changes, its peripartum dynamics and correlation with uric acid may reflect underlying metabolic-inflammation pathways. ΔBMI indices may offer a more individualized measure of weight dynamics in pregnancy research. Full article