Search Results (374)

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

This narrative review presents an updated overview of the etiology, pathophysiology, diagnostic approaches, and management strategies for Placenta Accreta Spectrum (PAS), with emphasis on clinical implications and current gaps in evidence. PAS is associated with substantial maternal morbidity and mortality, with reported maternal mortality rates approaching 7%. Affected patients often experience prolonged hospitalization, repeated surgical interventions, and long-term psychological and emotional consequences. The development of PAS is primarily attributed to impaired decidualization in areas of uterine scarring, resulting in abnormal adherence or invasion of chorionic villi into the myometrium. Optimal outcomes in high-risk pregnancies depend on early antenatal identification using characteristic pathological and imaging findings. Current evidence supports planned cesarean hysterectomy as the safest and most definitive treatment for most patients, whereas conservative and uterus-preserving approaches should be reserved for carefully selected cases managed in specialized centers. Further progress in PAS management requires standardized diagnostic criteria, prospective evaluation of conservative strategies, and improved access to multidisciplinary expertise. Full article

Background: SARS-CoV-2 infection during pregnancy has been associated with systemic inflammatory responses and placental pathology; however, the molecular mechanisms underlying placental involvement remain incompletely understood. The endocannabinoid system plays a critical role in placental development, immune regulation, and vascular homeostasis. Materials and Methods: Placental tissues were obtained from 20 healthy pregnant women and 20 women with confirmed SARS-CoV-2 infection who had recovered by the time of delivery. Demographic and laboratory parameters were recorded. Histopathological evaluation was performed using hematoxylin and eosin staining. Immunohistochemical analysis of cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) expression was conducted, supported by quantitative digital image analysis using QuPath. Network-based protein–protein interaction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore potential molecular mechanisms. Results: COVID-19-positive placentas exhibited prominent histopathological alterations, including increased fibrinoid deposition, syncytial knot formation, vascular congestion, and intervillous inflammatory cell infiltration. Systemic inflammatory and coagulation markers, particularly neutrophil percentage, C-reactive protein, D-dimer, and fibrinogen levels, were significantly elevated in the COVID-19 group. CNR1 and CNR2 expressions were markedly increased across multiple placental compartments, including decidual cells, trophoblastic layers, syncytial knots, and Hofbauer cells. Quantitative digital analysis confirmed significant upregulation of both receptors. Bioinformatic analysis revealed enrichment of endocannabinoid signaling, cAMP-related pathways, and inflammatory mediator regulation of TRP channels. Conclusions: The findings indicate that SARS-CoV-2 infection is associated with coordinated inflammatory, structural, and molecular alterations in the placenta. Upregulation of CB1 and CB2 suggests an active involvement of the endocannabinoid system in placental immune and vascular responses to COVID-19, highlighting its potential relevance for understanding placental pathology associated with maternal viral infections Full article

Female reproductive tract (FRT) disorders such as maternal conditions and gynecological cancers represent a significant global health burden. However, women’s health, and particularly locally acting therapies targeting the FRT, has historically been underprioritized in drug development and translational research. Developing safe and effective therapies requires a clear understanding of drug transport across FRT barriers. Conventional in vitro culture systems and animal studies fail to recapitulate the physiological complexity of the human FRT, including stratified mucosal architecture, functional mucus barriers, microbiome interactions, as well as dynamic hormonal regulation. Recently, organ-on-chip (OoC) microfluidic platforms, integrating human cells with precisely controlled perfusion, have emerged as advanced in vitro systems capable of recreating dynamic physiological microenvironments. This review summarizes the major anatomical and physiological barriers of the FRT, including the vagina, cervix, endometrium, and placenta, and discusses critical design considerations for the development of FRT-on-chip models. We highlight the advanced OoC developed to study infection, drug permeation, hormonal responses, and maternal–fetal interface dynamics. Finally, future perspectives are outlined, including the integration of immune components, vascularization strategies, and multi-organ systems to better simulate inter-organ communication. Collectively, these advances underscore the potential of FRT-on-chip models as predictive platforms for preclinical drug screening, toxicity evaluation, and personalized medicine. Full article

Exposure to poly- and perfluoroalkyl substances (PFASs) has been a cause for concern for decades due to evidence linking exposure to these substances with adverse health effects. Its widespread use in industrial and consumer products combined with their persistence in the environment poses a toxicological and regulatory challenge. Due to its ubiquity, resistance to degradation, and accumulation in biological systems, humans are exposed to a mixture of multiple PFASs, which complicates the analysis of exposure effects. As PFASs pose a risk to human health, it is crucial to study their impact during vulnerable periods, such as pregnancy. In this regard, understanding the impact of PFASs on the placenta is essential, as they can affect both pregnancy and the well-being of the developing fetus. This article reviews the current evidence linking PFAS exposure with altered placental function, focusing on the affected molecular pathways. Furthermore, we examine current methodologies for analyzing the effects of exposure to complex mixtures and explore how these approaches could be employed to evaluate the potential impact of such mixtures on placental function in the context of real-life exposure to these chemicals. Full article

The study aimed to determine whether placental lesions differ according to the duration of dystocia. Forty-seven placentas were obtained from 18 bitches that underwent emergency cesarean sections. For descriptive purposes, the cases were classified into four groups based on the duration of dystocia: Group A, up to 6 h; Group B, 6–11.9 h; Group C, 12–24 h; and Group D, more than 24 h. Forty-seven placentas were studied. Both macroscopic and microscopic characteristics were evaluated in each placenta. Descriptive data were presented, and logistic and multinomial regression models were used to assess whether dystocia duration (in hours) is associated with the presence and severity of placental macro- and microscopic lesions. An hour increment over the mean in the duration of dystocia showed a non-significant trend to increasing the presence of macroscopic necrosis (OR: 1.11, p = 0.09) and mineralization (OR: 1.10, p = 0.06), and it also increased the severity of macroscopic congestion (OR: 1.44; p = 0.01) and showed a non-significant trend to increasing the severity of polymorphonuclear neutrophil infiltrate (OR: 1.18; p = 0.06). These findings highlight the importance of early obstetric intervention in all cases of dystocia to minimize fetal hypoxia and improve neonatal outcomes. Moreover, the placenta could serve as a biomarker for fetal distress, as the presence of severe lesions indicates an increased risk for reduced neonatal survival. Full article

Toxic heavy metals, including cadmium (Cd) and lead (Pb), can build up in placental tissue or pass through the placental barrier, potentially harming fetal development. Therefore, the placenta can serve as a useful tool for assessing prenatal exposure to these harmful substances. Over the past several decades, Croatia has implemented a range of environmental and public health measures aimed at reducing exposure to Cd and Pb, including ratification of the World Health Organization Framework Convention on Tobacco Control (FCTC), ban on smoking in public places, intensified health education campaigns, and the complete phase-out of leaded gasoline in 2006. As a result, smoking prevalence among women and Pb levels in ambient air have declined substantially. This study reviews and analyzes existing literature on Cd and Pb levels in placental tissue of women in Zagreb, Croatia, in order to evaluate the effectiveness of these health and environmental policies and to identify persistent or emerging risks associated with toxic metal exposure during pregnancy by comparing placental Cd and Pb levels between smokers and nonsmokers across several time periods. Full article

Differentiation of villous cytotrophoblasts into syncytiotrophoblasts is essential for placental endocrine function and estradiol production. Caffeine consumption has been linked to altered estradiol levels, but its effects on human trophoblast differentiation remain incompletely understood. This study investigated the effects of caffeine on biochemical differentiation of human trophoblasts using BeWo cells and human placental explants. Cell viability and apoptosis were assessed using CCK-8 and in situ TUNEL assays. Differentiation-associated changes were evaluated by measuring CYP19A1 and its placenta-specific promoter transcript CYP19 I.1, at the mRNA level, while aromatase protein expression and estradiol production were assessed by Western blotting and ELISA, respectively. Exposure to 2 mM caffeine reduced BeWo cell viability, whereas 1 mM caffeine had no detectable effects on cell viability or apoptosis. At non-cytotoxic concentrations, caffeine significantly increased CYP19A1 mRNA expression under both basal and forskolin-stimulated conditions and elevated estradiol production. Similar transcriptional and endocrine responses were observed in human placental explants. Pharmacological inhibition demonstrated that caffeine-induced CYP19A1 transcriptional upregulation was dependent on PKA signaling, but not on PKC or MAPK pathways. These results indicate that caffeine can modulate trophoblast biochemical differentiation via PKA-dependent regulation of placental aromatase expression and estradiol synthesis. While these findings provide mechanistic insight into caffeine-mediated effects on trophoblast endocrine function, their relevance to physiological exposure levels and in vivo placental development warrants cautious interpretation. Full article

Background/Objectives: Maternal immune activation (MIA) increases the risk of Autism Spectrum Disorders (ASD). Experimental models demonstrate that maternal exposure to bacterial endotoxin or the viral mimic polyinosinic:polycytidylic acid [poly (I:C)] reliably recapitulates ASD-like behavioral abnormalities in offspring, yet the underlying neurobiological mechanisms linking MIA to altered neurodevelopment remain incompletely understood. Increasing evidence highlights the placenta as a critical mediator in shaping fetal brain development through immunological and hormonal regulation. Likewise, disruption of placental regulatory functions upon MIA may therefore represent a mechanistic pathway. Here, we investigated how alterations in placental cytokine profiles, innate immune cell composition, and endocrine outputs relate to neuroinflammation and neurogenesis in the offspring. Methods: Pregnant mice at gestational day 12.5 received a single intraperitoneal injection of poly (I:C). Placental macrophages, neutrophils, inflammatory cytokines, and nerve growth factor (NGF) expression were examined 72 h later. Neurodevelopmental outcomes, including microglial activity and neurogenic markers, were evaluated in mouse offspring at postnatal day (P) 1 and 6. Results: MIA induced a significant accumulation of monocytes and neutrophils in the placenta, which was associated with elevated levels of a broad spectrum of inflammatory mediators, including Th17-biased proinflammatory cytokines, chemokines, and adhesion proteins, in the placenta and amniotic fluid. In contrast, the placenta-derived NGF levels were significantly reduced. MIA induced strong and sustained microglial activation in the fetal and neonatal brain. This inflammatory milieu was accompanied by disrupted cortical neurogenesis, characterized by a marked increase in Ki67+ neuronal progenitor cells (NPCs) in the subventricular zone (SVZ), overproduction of early-born Tbr1+ neurons at P1, later-born Satb2+ neurons at P6. Conclusions: Collectively, these findings suggest that heightened Th17 inflammatory signaling, coupled with impaired placental endocrine function, contributes to dysregulated cortical neurogenesis in the offspring. Full article

Complex or difficult cesareans are associated with significant short- and long-term complications. The complication rate increases with the increasing number of cesareans, and the incidence of cesarean section is increasing. To accurately identify women at high risk of surgical difficulty during a cesarean, ultrasound, in addition to clinical assessment, can be used to evaluate many risk factors, including placenta previa, placenta accreta spectrum (PAS) disorders, fibroids, severe pelvic adhesions, and membranous fetal vessels. The role of preoperative ultrasound is to identify ultrasonographic signs of anatomic changes that may affect the risk of intraoperative complications in subsequent cesarean sections. It is important to look for maternal problems as well as fetal problems. Ultrasound is a well-established practice in obstetrical care as it is easily available, accessible, easy to perform, and well accepted by women. However, there are few studies on the role of preoperative ultrasound in the management of complex or difficult cesareans beyond the risk assessment of PAS. Currently, preoperative ultrasound is mostly performed in selected cases only, with the exception in some settings. The aim of this review article is to discuss the benefits and the use of ultrasound assessment before different types of complex or difficult cesareans. Whether ultrasound assessment should be performed before all cesarean sections will also be discussed. Full article

Microplastics (MPs) and nanoplastics (NPs) are widespread environmental contaminants with documented impacts on human health, particularly on the female reproductive system. Defined as polymeric fragments smaller than 5 mm, MPs (typically ranging from 1 µm to 5 mm) and NPs (smaller than 1 µm, often <100 nm) originate either from primary sources—intentionally manufactured for specific industrial applications—or from secondary sources through physical, chemical, or biological degradation of macroplastics. Human exposure occurs via multiple routes, including ingestion, inhalation, dermal absorption, and iatrogenic introduction, with growing evidence that these particles can accumulate in the ovaries, oocytes, and placental tissue. Experimental studies in rodents demonstrate that MPs and NPs induce oxidative stress, trigger inflammatory responses, and promote granulosa cell apoptosis, ultimately diminishing ovarian reserve and impairing folliculogenesis. Clinical and pilot human studies have confirmed the presence of MPs in placentas, umbilical cord blood, and meconium, indicating exposure from the earliest stages of development. Moreover, MPs and NPs may disrupt the hypothalamic–pituitary–ovarian axis, contributing to endocrine dysregulation and hormonal imbalance. Analytical methods such as Fourier-transform infrared spectroscopy, Raman spectroscopy, and scanning electron microscopy enable detection of these particles in biological samples, although methodological standardization remains insufficient. This paper summarizes current evidence on the exposure pathways, toxicological effects, and reproductive consequences of MPs and NPs in women. It further highlights existing research gaps and evaluates available analytical approaches to support future studies and develop strategies aimed at mitigating their detrimental impact on women’s reproductive health and fertility. Full article

Background/Objectives: Intrauterine growth restriction (IUGR) is a condition in which a fetus does not reach its normal growth potential and is associated with increased neonatal morbidity. Surveillance relies on cardiotocography, a biophysical ultrasound, and a Doppler assessment, but placental pathology remains insufficiently integrated into clinical evaluations. This study aimed to compare placentas from IUGR and normal pregnancies. Methods: This cohort included 34 pregnancies (16 IUGR, 18 controls) managed at Hunedoara County Hospital (Romania). The ultrasound and Doppler parameters were documented. The placentas were collected after delivery, fixed in formalin, and processed using standard histopathological protocols. The villous morphology and maternal vascular malperfusion features were assessed on H&E sections, focusing on syncytial knots, villous caliber reduction, stromal fibrosis, fibrin deposition, and infarctions. Immunohistochemistry for CD34, cytokeratin 7 (CK7), CD68, vascular endothelial growth factor (VEGF), and Hypoxian inducible factor 1 (HIF-1α)was performed using a semi-quantitative 0–3 scoring system. A statistical analysis was performed using chi-squared testing for categorical variables and t-tests for continuous variables. Results: The ultrasound evaluation showed an estimated fetal weight below the 10th percentile and abnormal Doppler indices in the IUGR group. The histopathology demonstrated a strong association between IUGR and villous abnormalities, including an increased number of syncytial knots, stromal fibrosis, a reduced villous caliber, and placental infarctions. The immunohistochemistry showed a marked overexpression of VEGF and HIF-1α and increased CD68-positive Hofbauer cells in IUGR placentas (p < 0.0001), while CD34 and CK7 displayed preserved strong staining in both groups. Conclusions: Placentas from IUGR pregnancies exhibited advanced maternal vascular malperfusion with consistent hypoxic and inflammatory changes, correlating with Doppler alterations. These findings highlight the diagnostic relevance of placental pathology in pregnancies with IUGR. Full article

Objective: This study evaluated the association of the uric acid/albumin ratio (UAR) and platelet indices—mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR)—in predicting hypervascularization in placenta accreta spectrum (PAS) and compared clinical and perinatal characteristics among PAS, placenta previa, and healthy pregnancies. Methods: This retrospective study included 229 pregnant women managed and delivered at a tertiary hospital (PAS, n = 76; previa, n = 77; healthy controls, n = 76) between January 2023 and January 2025. Hypervascularization was staged using the ultrasonographic PAS scoring system: PAS0 (placenta previa without hypervascularization), PAS1 (abnormal placental findings without hypervascularization), PAS2 (uterovesical hypervascularization), and PAS3 (extensive vascularity to the parametrial area). The final diagnosis and severity of PAS were confirmed intraoperatively according to the FIGO clinical classification criteria. Platelet indices and UAR were obtained from preoperative blood tests. Results: Compared with placenta previa (PAS0) and control groups, PAS1–3 cases had higher gravidity, parity, previous cesarean history, postpartum hemorrhage, hysterectomy, and transfusion rates (all p < 0.001). In the high hypervascularization subgroup (PAS2–3, n = 38), MPV (median 10.3 fL) and PDW (11.6%) were significantly lower than in low/absent hypervascularization cases (PAS0–1) (p = 0.001, p = 0.001, respectively). UAR showed no significant difference (p = 0.891). Conclusions: Lower MPV and PDW were associated with hypervascularization in PAS and may serve as non-invasive adjunctive markers for risk stratification. Their predictive performance was modest, and UAR had no diagnostic value, likely due to physiological changes in pregnancy. Further prospective, multicenter research is needed to validate these findings. Full article

Background and Objectives: Despite the development of medicine, there is no clearly established scheme for the prediction of intra-amniotic infection (IAI). In this study, evaluation of some predictors of IAI confirmed in histopathological examination was performed. Materials and Methods: The study population included 70 patients all giving birth by cesarean section divided into two groups: study (n = 34) consisting of patients with histologically confirmed IAI and control (n = 36) without IAI. Biological material included the mother’s venous blood to determine C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) concentrations; vaginal discharge to determine IL-6; cervical canal swabs to perform cultures for bacteria and fungi and polymerase chain reaction (PCR) for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis; amniotic fluid to perform cultures for aerobic and anaerobic bacteria and PCR for atypical pathogens, and to determine glucose, IL-6, and PCT concentrations; umbilical cord blood to determine PCT, CRP, Il-6 and blood culture. A fragment of the placenta and fetal membranes was taken for histopathological assessment of the inflammatory infiltrate. Results: Mothers’ serum CRP assessments as well as serum PCT assessments are of poor diagnostic value in the prediction of IAI confirmed in histopathological examination. Conclusions: The best predictive values of IAI confirmed in histopathological examination were amniotic fluid glucose and vaginal fluid IL-6 determinations. Full article

Background: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is costly, and can cause significant morbidity, including distal limb ischaemia due to thrombus formation. We believe that internal iliac ligation under direct vision is a safe option to control bleeding. We sought to evaluate the short- and long-term outcomes relating to this technique compared to IR. Methods: This is a mixed-methods cohort study of women with severe PAS who underwent hysterectomy with either surgical devascularisation, as part of the Soleymani and Collins (SAC) technique, or IR insertion of internal iliac balloon catheters, in a UK tertiary referral centre for PAS between 2011 and 2022. Only women with intraoperative diagnosis of very severe PAS (FIGO stage 3b & c) were included in this study. Results: Of the 22 women invited to participate in the long-term component of the study, 59% agreed. Women in the surgical devascularisation group experienced no adverse short or late sequelae related to internal iliac arterial ligation. Pelvic devascularisation (11 patients, 41%) demonstrated a reduction in median estimated blood loss, 1600 millilitres vs. 2500 millilitres in the IR balloon catheter group (p = 0.04). Conclusions: We have demonstrated that the SAC technique for surgical devascularisation is a safe method for achieving haemorrhage control during caesarean hysterectomy for severe PAS. It also appears to be at least as effective at haemorrhage control as IR balloon occlusion of the internal iliac vessels. Full article