Search Results (484)

Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes. Full article

Background: Presence of milk, fruits, eggs, fish, nuts and wheat antigens in the amniotic fluid is described in the literature. Studies show a contradictory relationship between maternal exposure to allergens and early sensitization of the fetus to allergens. Hemochorionic type of the human placenta allows for easier transfer of nutrients and antibodies from the mother’s blood to the fetal circulation through the direct contact of maternal blood with the fetal chorion. During the third trimester of pregnancy, immunoglobulin G (IgG) is actively transferred through the placenta into the fetal via neonatal FcRN receptor (FcRN). In addition, monomeric immunoglobulin E (IgE) cannot cross the placenta Aim: The objective of our study is to track intrauterine sensitization to essential food proteins at birth in umbilical cord blood in mothers with established peripheral blood eosinophilia and in their infants using allergen-specific IgE and IgG. Methods: An observational study was carried out in a cohort of 22 mothers with eosinophilia and their babies. Differences in expression between groups were assessed. Blood samples were collected to determine serum IgE and IgG specific to a set of inhalant and food allergens. Results: We did not find a significant correlation between specific IgE to cow’s milk (p = 0.857), egg white (p = 0.926) and egg yolk (p = 0.096) in umbilical cord blood and maternal blood samples taken immediately before birth. Spearman’s correlation of the specific IgE and IgG in umbilical cord blood showed no dependence between the two variables. In contrast, statistical analysis showed that maternal eosinophilia in peripheral blood could be a risk factor for the development of allergy in the offspring (χ², p = 0.0347). However, given the small number of patients, this claim needs to be confirmed with further studies. Conclusions: Due to the functional immaturity of the developing immune system of the fetus, the generation and maintenance of an independent immune response to allergens are incomplete. Maternal IgG (specific) passes to the baby and high maternal IG to a specific allergen reduces babies IgE production. In addition, low maternal specific IgG may promote IgE production in the baby under the influence of microenvironmental factors (cytokine background). The main limitation of our study is the small number of patients. Further research is needed in this direction to clarify the mechanisms and risk factors for early sensitization in newborns. Full article

Spina bifida (SB) is a congenital malformation of the central nervous system (CNS), resulting from incomplete closure of the neural tube (NT) during early embryogenesis. Myelomeningocele (MMC), the most severe form of SB, leads to progressive neurological, orthopedic, and urological dysfunctions due to both NT developmental failure and secondary intrauterine injury (“two-hit hypothesis”). Prenatal repair of MMC has progressed considerably since the Management of Myelomeningocele Study (MOMS, 2011) trial, which showed that open fetal surgery can decrease the need for shunting and improve motor function, although it carries significant maternal risks. To address these limitations, minimally invasive techniques have been developed, with the goal of achieving similar benefits for the fetus while reducing maternal morbidity. Recent research has shifted toward regenerative strategies, integrating mesenchymal stem cells (MSCs), bioengineered scaffolds, and cell-derived products to move beyond mere mechanical protection toward true NT repair. Preclinical studies in rodent and ovine models have shown that amniotic- and placenta-derived MSCs exert neuroprotective and immunomodulatory paracrine effects, promoting angiogenesis, modulating inflammation, and supporting tissue regeneration. Minimally invasive, cell-based interventions such as Transamniotic Stem Cell Therapy (TRASCET), in preclinical rodent models, offer the possibility of very early treatment without hysterotomy, although translation remains limited by the lack of large-animal validation and long-term safety data. In parallel, advances in biomaterials, nanostructured scaffolds, and exosome-based therapies reinforce a regenerative paradigm that may improve neurological outcomes and quality of life in affected children. Ongoing translational studies are essential to optimize these approaches and define their safety and efficacy in clinical settings. This review provides an integrated overview of embryological mechanisms, diagnostic strategies, and prenatal therapeutic advances in SB treatment, with emphasis on prenatal repair, fetal surgery and emerging regenerative approaches. Full article

Maternal nutrition during gestation profoundly influences fetal growth, organogenesis, and long-term offspring performance through developmental programming. Among the molecular mechanisms responsive to maternal nutrient availability, one-carbon metabolism plays a central role by integrating folate, methionine, choline, and vitamin B₁₂ pathways that regulate methylation, nucleotide synthesis, and antioxidant defense. These processes link maternal nutritional status to epigenetic remodeling, cellular proliferation, and redox balance during fetal development. Mitochondria act as nutrient sensors that translate maternal metabolic cues into bioenergetic and oxidative signals, shaping tissue differentiation and metabolic flexibility. Variations in maternal diet have been associated with shifts in fetal amino acid, lipid, and energy metabolism, suggesting adaptive responses to constrained intrauterine environments. This review focuses on the molecular interplay between one-carbon metabolism, mitochondrial function, and metabolomic adaptation in developmental programming of ruminant livestock. Understanding these mechanisms offers opportunities to design precision nutritional strategies that enhance fetal growth, offspring productivity, and long-term resilience in livestock production systems. Full article

Background/Objectives: Female tubal factor infertility is a major clinical challenge. While surgical repair of the fallopian tubes remains the traditional standard, biological fibrin sealants have been proposed to reduce tissue trauma and improve reproductive outcomes. Methods: We conducted database searches of PubMed/MEDLINE, EMBASE and Google Scholar until 31 August 2025, using the keywords “tubal anastomosis”, “tubal reanastomosis,” “tubal reanastomosis”, “uterine horn anastomosis”, “fibrin glue”, “fibrin sealant”, “biological sealant”, “tissue adhesive”, “rabbit”, “rat” and “sterilization reversal.” Reference lists of retrieved articles have been examined to find studies which tested end-to-end tubal (or small-animal uterine horn) anastomosis through biological adhesives with or without additional components to evaluate patency success, fertility results and adhesion formation. Results: Thirteen studies met the inclusion criteria (eleven animal; two human). Rat and rabbit models demonstrated that fibrin sealants with intraluminal splints and one-to-two anchoring sutures produced results comparable to microsutures for patency (tubal patency rates of 75–100%) and pregnancy success (pregnancy rates of 60–83%) while reducing surgical time and decreasing peritubal adhesions. The success rates of the procedures depended on the anastomosis locations. Isthmic–isthmic anastomosis produced better results than ampullary repairs which tended to fail or develop stenosis. Fibrin sealant-only repairs without splinting were associated with lower patency (almost 60%) despite acceptable histologic healing. Human data showed similar pregnancy rates (intrauterine pregnancy in about 40–50% of women) and tubal patency but no consistent decrease in adhesions. Ectopic pregnancy rates ranged from 9 to 11%. Conclusions: Fibrin sealants are useful adjuncts to microsurgical tubal repair, but they should not replace the basic repair procedures. The effectiveness of this procedure is dependent on three critical factors: precise segment alignment, proper use of splints and stents, and selection of segments with comparable caliber. In a personalized-medicine framework, fibrin-assisted reanastomosis may offer a tailored option for selected women who desire natural pregnancy. Modern standardized research is required to define indications and analyze how the adaptation of fibrin sealants in minimally invasive procedures affect reproductive outcomes, ectopic pregnancy rates, and adhesion development. Full article

Background: Testicular dysgenesis syndrome (TDS) is a complex disorder of the male reproductive system related to disfunction of the fetal testis. The clinical features of TDS may be evident at birth or infancy (cryptorchidism, hypospadias and/or reduced anogenital distance) or occur later in adulthood (testis cancer, infertility). Genetic background seems to be important for genetic predisposition, with new genes being associated with components of the syndrome in last years. Interestingly, the incidence of clinical manifestations of TDS has been increasing in many countries in recent decades, suggesting that genetic predisposition alone cannot explain this trend. Consequently, the hypothesis of multifactorial etiopathogenesis is becoming increasingly accepted nowadays, with environmental factors probably acting during early developmental stages in genetically predisposed individuals. Methods: In this narrative review, we aim to critically evaluate genetic and non-genetic factors involved in the pathogenesis of TDs. Results: Important associations with intrauterine growth disorders and maternal diseases (overweight/obesity and diabetes) as well as lifestyle factors (e.g., smoking and alcohol abuse) were found. In such context, endocrine disruptors probably play a major role. These substances are widely used in industry and can exert estrogenic and antiandrogenic effects, potentially interfering with the development of the fetal gonad. Conclusions: Considering their possible impact on male sexual health, more attention should be focused on maternal modifiable factors to confirm with prospective studies the mixed results of available evidence. Full article

Background: Ectopic pregnancy (EP) is a potentially life-threatening condition, often associated with acute abdominal pain and hemoperitoneum. Certain conditions, such as adenomyosis and the use of long-acting reversible contraceptives (LARC), may represent risk factors for the development of ectopic pregnancy. Management is tailored according to hemodynamic stability, reproductive desires, and associated comorbidities. Case Presentation: We report the case of a 39-year-old Caucasian woman with a history of adenomyosis and heavy menstrual bleeding (HMB) treated with a levonorgestrel-releasing intrauterine system (LNG-IUS). She presented to the emergency department with acute abdominal pain, vaginal bleeding, and a rising serum β-human Chorionic Gonadotrophin (β-hCG > 4000 mIU/mL). Transvaginal ultrasound revealed an adnexal mass (24 mm × 19 mm) consistent with a right tubal ectopic pregnancy, associated with hemoperitoneum. The patient, who expressed a desire for definitive sterilization, underwent laparoscopic bilateral salpingectomy. The procedure was uneventful with minimal intraoperative blood loss. Histopathological examination confirmed the diagnosis of right tubal ectopic pregnancy. Literature Review: A case report prompted a focused search of MEDLINE and Scopus (2015–2025) on ectopic pregnancy in users of levonorgestrel-releasing intrauterine systems. Eight eligible case-report studies assessing ectopic pregnancy type and device positioning were ultimately included. Conclusions: This case highlights the importance of early diagnosis of ectopic pregnancy, paying attention to any comorbidities, particularly adenomyosis, the role of minimally invasive surgery, and the possibility of adapting surgical management to the patient’s reproductive wishes. Full article

Background/Objectives: Fetal growth restriction (FGR), formerly known as intrauterine growth retardation (IUGR), is defined as a fetus’ failure to reach its genetically predetermined growth potential. FGR has also been implicated in the development of autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), though strong supporting literature has yet to be published. This study aims to review the existing associations between FGR and autism spectrum disorder or attention-deficit hyperactivity disorder as studied in relevant literature, as well as the mechanisms that provide explanation of that association. Methods: We used a combination of the terms ‘Autism spectrum disorder’ OR ‘Attention deficit hyperactivity disorder’ OR ‘neurodevelopmental disorders’ AND ‘intrauterine growth retardation (IUGR)’ OR ‘fetal growth restriction (FGR)’ in an electronic search of PubMed/MEDLINE and Scopus databases. Results: After evaluating the existing literature, we found only a few studies assessed the risk of developing ASD or ADHD in IUGR/FGR children. Neurodevelopmental disorders have generally been linked to very low birth weight, small for gestational age neonates (SGA), prematurity, somatic mutations, and intrauterine caffeine and alcohol exposure. While available evidence supports the notion that IUGR/FGR is related to cognitive impairment and behavioural disorders, the association with ASD or ADHD remains elusive due to the marked variability in the reported outcomes. Few studies have reported a respective higher risk for autism spectrum disorders, yet most of them have failed to identify a statistically significant correlation. Conclusions: While autism spectrum disorders and attention deficiency disorder have been generally associated with FGR children, the existing body of literature offers limited evidence to support this theory. Full article

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are obstetric complications associated with placental dysfunction, which represent a public health problem due to high maternal and fetal morbidity and mortality. Early detection is crucial for timely interventions. Therefore, this study proposes the development of models based on fuzzy cognitive maps (FCM) optimized with metaheuristic algorithms (particle swarm optimization (PSO) and genetic algorithms (GA)) for the prediction of PE and IUGR. The results showed that FCM-PSO applied to the PE dataset achieved excellent performance (accuracy, precision, recall, and F1-Score = 1.0). The FCM-GA model excelled in predicting IUGR with an accuracy and F1-Score of 0.97. Our proposed models outperformed those reported in the literature to predict PE and IUGR. Analysis of the relationships between nodes allowed for the identification of influential variables such as sFlt-1, sFlt-1/PlGF, and uterine Doppler parameters, in accordance with the pathophysiology of placental disorders. FCM optimized with PSO and GA offer a viable clinical alternative as a medical decision support system due to their ability to explore nonlinear relationships and interpretability of variables. In addition, they are suitable for scenarios where low computational resource consumption is required. Full article

Background: Complete fetal atrioventricular block (CAVB) is a rare but life-threatening condition, occurring in approximately 1–2% of pregnancies associated with maternal anti-Ro/SSA antibodies. The transplacental migration of anti-Ro/SSA and anti-La/SSB antibodies damages the fetal cardiac system, leading to sustained bradycardia, cardiomyopathy, fetal hydrops, and intrauterine fetal demise. Despite the use of fluorinated corticosteroids or β-agonists, therapeutic efficacy remains limited once a complete block is established. Case Presentation: We present the case of a 35-year-old primigravida with a pregnancy achieved through in vitro fertilization (IVF). At 20 weeks of gestation, she was referred to our emergency unit due to persistent fetal bradycardia. Fetal echocardiography confirmed CAVB with a ventricular rate of 64 bpm. Maternal serologic testing was positive for anti-Ro/SSA and anti-La/SSB antibodies, suggesting an autoimmune etiology. Treatment with oral dexamethasone and salbutamol was initiated, but follow-up echocardiography at 24 weeks showed worsening cardiac status, including reduced ventricular rate of 59 bpm, cardiomegaly, and pericardial effusion. Intrauterine fetal death occurred at 25 weeks of gestation. Management and Outcome: Four months postpartum, the patient underwent a minor salivary gland biopsy. Histopathological evaluation confirmed the diagnosis of primary Sjögren’s syndrome. Conclusions: This case illustrates the severe consequences of autoimmune-mediated CAVB and the limited effectiveness of available treatments once a complete block has developed. It underscores the importance of early fetal rhythm surveillance and targeted maternal autoimmune screening—particularly before assisted reproduction, where structured preconception evaluation offers an opportunity for earlier recognition and risk stratification. Earlier detection may improve counseling and management strategies in future pregnancies. Full article

Objectives: This study aimed to evaluate whether first-trimester metabolic markers—including the triglyceride-glucose (TyG) index and lipid-related ratios (TG/HDL-c, LDL-c/HDL-c, and TyG/BMI)—could predict the development of late-onset preeclampsia, and to assess their associations with birthweight and birth length. Methods: A retrospective cohort study was conducted on 306 pregnant women (153 with late-onset PE and 153 normotensive controls). Demographic and clinical data, including maternal lipid profiles, TyG index, and other biochemical markers, were collected during the first trimester. Statistical analyses, including Mann–Whitney, two-sided t-tests, and receiver operating characteristic curves (ROC), were performed to assess the predictive value of the TyG index and other ratios in predicting late-onset PE. Results: Significant differences between the PE and control groups were observed in delivery method, birthweight, and birthlength (p < 0.05). ROC analysis revealed that the TyG index had an area under the curve (AUC) of 0.79, with a sensitivity of 69.3% and specificity of 75.8%. The TyG index was inversely associated with birthweight (ρ = −0.288) and gestational age at delivery (ρ = −0.218), while positively correlating with systolic blood pressure (ρ = 0.441). Conclusions: The TyG index, along with TG/HDL and LDL-c/HDL ratios, demonstrated predictive value for late-onset PE. These findings suggest that elevated TyG index levels may contribute to adverse pregnancy outcomes such as intrauterine growth restriction and preterm delivery. First-trimester lipid profiles and the TyG index may serve as valuable markers for early prediction of late-onset PE. Full article

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Background/Objectives: The objective was to establish whether particular SPD risk factors are correlated with particular SPD patterns and whether these factors affect the motor development of children Methods: The study procedures included medical examinations, conducted by a pediatrician/child neurologist, and evaluations, performed by a physiotherapist/sensory integration specialist, which were performed on the study group. Results: The study included 156 Caucasian children with SPD aged 3 to 12 years. The results of this study demonstrate that serological conflict shows correlations with taste, smell, and visual hyposensitivity. Fetal heart rate fluctuations, indicated in CTG, are correlated with tactile hypersensitivity and vestibular hypersensitivity, and cesarean delivery is correlated with auditory hyposensitivity. Incubator care is correlated with tactile hypersensitivity and auditory hyposensitivity. Intrauterine infections are correlated with vestibular hypersensitivity. Delayed motor development is correlated with bed rest in the third trimester of pregnancy, intrauterine infections, and incubator care. Conclusions: We conclude that children’s development must be monitored scrupulously in particular areas of sensory processing with regard to any of the abovementioned risk factors occurring in affected children. It is important to pay special attention to intrauterine infections, bed regimes in the third trimester of pregnancy, and incubator care, because these factors may have a negative impact on motor development. 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

High doses of ionizing radiation during prenatal development can cause growth restriction, or a decrease in growth of the developing offspring. This outcome of intrauterine growth restriction (IUGR) can predispose the offspring to lifelong health outcomes, which is referred to as developmental programming. The role of the placenta in radiation-induced IUGR was investigated using a mouse model. Pregnant BALB/cAnNCrl mice were externally irradiated with 1.82 Gy x-ray irradiation on gestational day 14.5. Fetoplacental units were collected on gestational day 18.5, and growth restriction was observed in irradiated offspring. Whole placenta samples from growth restricted and sham-irradiated groups were analyzed via RNA-sequencing analysis. Differential gene expression (DEG) analysis revealed a total of 166 DEGs in the irradiated samples. Validation of these DEG findings were completed using RT-qPCR analysis. Gene ontology (GO) analysis of the DEGs supported the involvement of autoimmune response and dysregulation in retinol (vitamin A) metabolism in the placenta. Upstream prediction analysis identified a number of potential regulators responsible for the DEG profiles including Nppb, Myod1 and genes of the classic complement system (Complement C1q chains C1qa, C1qb, C1qc). Overall, these findings present an overview of the dysregulation in the mouse placenta following an acute, high-dose radiation exposure. Full article