Search Results (154)

Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells and their effective medical applications has intensified research into spinal cord regeneration. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Methods: Our study involved a microsurgical dorsal myelotomy in fetal rats. The development of pioneering long primary afferent axons during early gestation was examined long after birth. Results: A single cut triggered the intrinsic ability of the dorsal root ganglion (DRG) neurons to reprogram. Susceptibility to hypoxia caused the axons to stop developing. However, the residual axonal outgrowth sheds light on the intriguing temporal and spatial events that reveal long-distance CNS regeneration. The altered phenotypes displayed axons of varying lengths and different features, which remained visible throughout life. The previously designed developmental blueprint was crucial for interpreting these enigmatic features. Conclusions: This research into immaturity enabled the exploration of the previously impenetrable domain of early life and the identification of a potential missing link in CNS regeneration research. Central axon regeneration appeared to occur much faster than is generally believed. The paradigm provides a challenging approach for exhaustive intrauterine reprogramming. When the results demonstrate pre-clinical effectiveness in CNS regeneration research, the transformational impact may ultimately lead to improved outcomes for patients with spinal cord injuries. Full article

Background: The worldwide prevalence of FGR is about 13% and can lead to various adverse perinatal outcomes, including preterm birth, stillbirth, and neonatal mortality. Hypoxia-Inducible Factor-1 (HIF-1) is an important regulator of oxygen homeostasis in humans and is crucial for placental development. The aim of this study is to determine the pattern of HIF-1A expression in placenta, and to correlate its association with preeclampsia, fetal growth restriction and adverse perinatal outcomes. Methods: This study comprised a total of 158 cases with 42 cases of mother having babies with fetal growth restriction (FGR), 39 cases of mother with preeclampsia (PE), 35 cases of mother with preeclampsia and fetal growth restriction and 42 controls. The expression of HIF-1A was evaluated in various placental cell types, including cytotrophoblasts, syncytiotrophoblasts, fetal endothelial cells, maternal endothelial cells, and decidual cells. Results: The expression of HIF-1A in placental decidual cells of mother with FGR (21/42, 50%, p < 0.0001), PE (25/39, 64.1%, p < 0.0001) and PE with FGR (12/35, 34.3%, p < 0.0001) were significantly increased compared to controls (1/42). Intriguingly, HIF-1A expression was significantly reduced in the placental cytotrophoblasts and syncytiotrophoblasts of mother with PE and FGR (2/35, 5.7%) compared to PE alone (11/39, 28.2%) (p = 0.0142). Conclusions: We found that increased HIF-1A expression in the nuclei of decidual cells was observed in the mothers of babies with FGR, both with and without PE. While HIF-1A expression in the cytotrophoblasts and syncytiotrophoblasts was significantly reduced between mothers with PE and mothers with PE and FGR. This suggests HIF-1A expression might play a role in the pathogenesis of FGR. Full article

Prenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothelial integrity during development. Exposure to PH disrupts NO-related signaling pathways, leading to endothelial dysfunction, mitochondrial damage, and an escalation of oxidative stress—all of which exacerbate cardiac injury and trigger cardiomyocyte apoptosis. The excessive generation of reactive nitrogen species drives nitrosative stress, thereby intensifying inflammatory processes and cellular injury. In addition, the interplay between NO and hypoxia-inducible factor (HIF) shapes adaptive responses to PH. NO also modulates the synthesis of heat shock protein 70 (HSP70), a critical factor in cellular defense against stress. This review emphasizes the involvement of NO in cardiovascular injury caused by PH and examines the cardioprotective potential of NO modulators—Angiolin, Thiotriazoline, Mildronate, and L-arginine—as prospective therapeutic agents. These agents reduce oxidative stress, enhance endothelial performance, and alleviate the detrimental effects of PH on the heart, offering potential new strategies to prevent cardiovascular disorders in offspring subjected to prenatal hypoxia. Full article

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

In this study, thirty female dogs, aged one to five years and varying in weight, in the last week of gestation were evaluated. The animals were divided into two groups: GC, which comprised twenty-two bitches undergoing elective cesarean section, and GD, which consisted of eight dogs requiring therapeutic cesarean section as a treatment to dystocia. We found that cortisol levels in the amniotic fluid were significantly higher in pups delivered via elective cesareans (mean: 9.86 ng/mL) compared to those from therapeutic c-sections (mean: 4.11 ng/mL). This observation contrasted with previous studies that reported lower cortisol levels in elective procedures, suggesting complexities in the physiological responses to different delivery methods that warrant further investigation. Notably, our study observed no significant association between amniotic fluid meconium presence and other distress markers, indicating that meconium may be more closely associated with fetal maturation rather than distress (p > 0.05). Neonatal viability (Apgar score) revealed that 92.86% of the neonates from elective procedures demonstrated no distress shortly after delivery, contrasting with 56.25% in therapeutic c-section. Fetal distress can be a direct consequence of dystocia caused by various stressors, such as pain and hypoxia. These factors can impair the fetus’ ability to adapt to extrauterine life, often leading to lower Apgar scores. Notably, neonatal weight was directly related to fetal cortisol levels, while no significant associations were noted between the litter size or birth order and cortisol concentrations, irrespective of the delivery type. These findings underscore the need for ongoing investigation into the relationships between cesarean delivery types, maternal and neonatal stress markers, and resultant health outcomes, aiming to enhance care strategies for expectant canine mothers and their puppies. Full article

Background: Among patients with congenital heart disease, particularly those with a history of undergoing the Fontan operation, pregnancy presents a significant maternal–fetal risk, especially when complicated by severe valvular dysfunction. Lung reperfusion syndrome (LRS) is a rare but life-threatening complication occurring following valve intervention. Multidisciplinary management, including by Cardio-Obstetrics teams, is essential for optimizing outcomes in such high-risk cases. Methods: We present the case of a 37-year-old pregnant patient with previously repaired tetralogy of Fallot (via the Fontan procedure) who presented at 24 weeks gestation with worsening severe pulmonary stenosis and right-ventricular dysfunction. The patient had been lost to cardiac follow-up for over a decade. She experienced recurrent arrhythmias, including supraventricular and non-sustained ventricular tachycardia, prompting hospital admission. A multidisciplinary team recommended transcatheter pulmonic valve replacement (TPVR), performed at 28 weeks’ gestation. Results: Post-TPVR, the patient developed acute hypoxia and hypotension, consistent with Lung Reperfusion Syndrome, necessitating intensive cardiopulmonary support. Despite initial stabilization, progressive maternal respiratory failure and fetal compromise led to an emergent cesarean delivery. The neonate’s neonatal intensive care unit (NICU) course was complicated by spontaneous intestinal perforation, while the mother required intensive care unit (ICU)-level care and a bronchoscopy due to new pulmonary findings. She was extubated and discharged in stable condition on postoperative day five. Conclusions: This case underscores the complexity of managing severe congenital heart disease and valve pathology during pregnancy. Lung reperfusion syndrome should be recognized as a potential complication following TPVR, particularly in pregnant patients with Fontan physiology. Early involvement of a multidisciplinary Cardio-Obstetrics team and structured peripartum planning are critical to improving both maternal and neonatal outcomes. Full article

A total of 30 hydropic fetuses, including 25 cases from published reports and 5 from our own series, were reviewed, validated, and analyzed. This review yielded the following key findings: (1) Unlike most cases of nonimmune hydrops fetalis (NIHF), hydrops caused by syphilis is not only preventable but also treatable, with complete resolution possible when appropriately managed. (2) Syphilis-associated hydrops carries a poor prognosis if timely and appropriate treatment is not administered. (3) Based on limited data, intravenous penicillin G is probably more effective than intramuscular benzathine penicillin in treating hydropic fetuses. (4) Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are increasingly used as a reliable and noninvasive tool for assessing fetal anemia, determining the need for intrauterine transfusion (IUT), and monitoring treatment response. (5) A significant number of cases did not receive prenatal treatment due to false-negative serologic results caused by the prozone effect, as well as the omission of syphilis from the differential diagnosis of NIHF, leading to missed prenatal diagnoses. (6) IUT may help mitigate cellular damage in developing vital organs caused by anemic hypoxia, particularly while awaiting the effects of medical treatment. In conclusion, the modern approach to managing this ancient disease includes: (1) prioritizing intensive intravenous penicillin G therapy over conventional intramuscular benzathine penicillin G; (2) utilizing MCA-PSV in conjunction with other indicators of anemia to monitor its severity; and (3) implementing IUT to prevent anemic hypoxic injury in cases where the hematocrit falls below 30%. Full article

Objective: Premature placental calcification (PPC) has been implicated in adverse perinatal outcomes, yet its clinical significance remains controversial. This meta-analysis aimed to quantitatively synthesize current data on the association between PPC, defined as grade 3 placental calcification before 36⁺⁶ weeks of gestation and adverse perinatal outcomes. Data Sources: A systematic search was conducted in MEDLINE, Scopus and The Cochrane Library from inception until 11 March 2025, to identify eligible studies. Study Eligibility Criteria: Observational studies including singleton pregnancies with PPC diagnosed via ultrasonography between 28⁺⁰ and 36⁺⁶ weeks of gestation and comparing them with pregnancies with Grannum grade 0, 1, or 2 placentas were considered eligible. Methods: Study quality was assessed using the Newcastle−Ottawa Scale, and the risk of bias was evaluated with the Quality In Prognosis Studies tool. The primary outcomes were small-for-gestational-age (SGA) neonates and preeclampsia. Heterogeneity was assessed using Cochran’s Q test and the I² statistic. Meta-analyses were conducted using a random-effects model, with outcomes reported as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results: In total, nine cohort studies were included. PPC was associated with an increased risk of SGA (RR, 1.99; 95% CI, 1.46−2.70), preeclampsia (RR, 5.27; 95% CI, 2.24−12.40), fetal growth restriction (RR, 2.31; 95% CI, 1.30−4.09), preterm delivery (RR, 2.11; 95% CI, 1.00−4.45), suspected fetal hypoxia (RR, 1.71; 95% CI, 1.13–2.56), low 5 min Apgar score (RR, 2.28; 95% CI, 1.50−3.44) and neonatal intensive care unit admission (RR, 1.80; 95% CI, 1.02−3.18). No significant associations were found with fetal or neonatal death (RR, 2.75; 95% CI, 0.87−8.71), cesarean delivery (RR, 1.26; 95% CI, 0.90−1.78), gestational diabetes mellitus (RR, 1.17; 95% CI, 0.81−1.70), neonatal resuscitation (RR, 1.04; 95% CI, 0.92−1.16), birthweight (MD, −187.46 g; 95% CI, −413.14 to +38.21), or gestational age at birth (MD, −0.62 weeks; 95% CI, −1.36 to +0.11). A sensitivity analysis excluding high-risk-of-bias studies yielded consistent results. Conclusions: PPC is associated with several adverse perinatal outcomes, including SGA and preeclampsia. While the clinical significance of placental grading has remained limited in recent years, this study has shown that PPC may serve as an early indicator of placental insufficiency, warranting enhanced fetal surveillance and risk assessment in affected pregnancies. Further research is needed to refine its prognostic utility and integration into obstetric practice. Full article

Clear-cell renal cell carcinoma (ccRCC) is associated with the mutated von Hippel–Lindau (VHL) gene leading to the activation of hypoxia-inducible factor 1A (HIF1A) and subsequent overexpression of erythropoietin (EPO). We analyzed tumor and healthy tissues from 43 ccRCC patients after radical nephrectomy and cultured 786-O (biallelic VHL inactivation) and Caki-1 (wild-type VHL) cells in normal (21% O₂) and low oxygen (3% O₂) with 10% and 2% fetal bovine serum (FBS). DNA sequencing, including Sanger sequencing, MLPA and LOH, revealed 27 somatic mutations of VHL in ccRCC. HIF1A protein showed decreased or no expression in tumors compared to healthy tissue, independent of VHL alteration. The 786-O cells showed increased HIF1A protein expression after 48 h under low oxygen and 10% FBS. EPO and erythropoietin receptor (EPOR) were significantly decreased in ccRCC without HIF1A expression. EPO mRNA increased in the 786-O cells at 3% O₂ after 48 h, while the Caki-1 cells had low or no EPO expression. Hypoxia increased EPOR mRNA in the Caki-1 cells at 10% FBS, but decreased in the 786-O cells at 2% FBS after 48 h. JAK2/STAT5A activity was increased only in HIF1A-positive tumors. These results suggest that EPO/EPOR activation in ccRCC is mainly driven by low oxygen, not VHL regulation of hypoxia-related responses. Full article

Background: Chronic venous disease (CVD) is a vascular disorder common among pregnant women, due to the impairment in the venous function associated with the mechanical, hemodynamical, and hormonal changes that occur during pregnancy. CVD is linked to venous hypertension, inflammation, oxidative stress, and hypoxia, which alter placental structure and function, as demonstrated in previous works. The placenta fulfills several roles in fetal development and maternal well-being by mediating nutrient exchange; acting as a mechanical, chemical, and immunological shield; and producing essential hormones, making it crucial to investigate the effects of CVD in this organ. Patients and methods: This work specifically analyzes the gene expression of circadian markers (CLOCK, BMAL1, PER1, and PER2), epigenetic regulators (HAT1 and associated molecules like histones H3, H4, RBBP7, and ASF1), and the anti-aging protein KLOTHO in placental tissue of pregnant women with CVD (CVD-PW, N = 98) compared to healthy pregnant controls (HC-PW, N = 82), using RT-qPCR and immunohistochemistry (IHC) to determine protein expression. Results: Our study demonstrates that the placentas of CVD-PW exhibit the reduced gene and protein levels of circadian regulators (clock, bmal1, per1, and per2), increased expression of hat1 and related proteins (h3, h4, rbbp7, and asf1), and decreased klotho expression, indicative of accelerated aging. Conclusions: These findings highlight profound molecular disturbances in the placentas of women with CVD, offering insights into the disease’s pathophysiology and potential implications for maternofetal well-being. While this study deepens our understanding of the relationship between CVD and placental dysfunction, further research is required to fully elucidate these mechanisms and their long-term effects. Full article

Fetal hypoxia is a condition that is caused by insufficient oxygen supply to the fetus and poses serious risks, including abnormalities, birth defects, and potential mortality. Cardiotocography (CTG) monitoring is commonly used to identify fetal distress, including hypoxia, by categorizing cases as normal or hypoxia. However, traditional CTG interpretation, usually performed visually by experts, can be subjective and error-prone, resulting in observer variability and inconsistent outcomes. It highlights the need for an automated and objective diagnostic system to assist clinicians in interpreting CTG data more accurately and consistently. In this research, a fetal hypoxia diagnosis system is proposed based on CTG signals. The CTG dataset is first transformed into the time-frequency domain using instantaneous frequency and using common spatial pattern (CSP) for feature extraction. Finally, the extracted features are then used to train and evaluate four machine learning models for classification with a cross-validation 5-fold methodology. Objective criteria (pH values, BDecf, Apgar 1, and Apgar 5) and expert voting as a subjective criterion were used to classify the fetus as normal or hypoxia. The SVM model outperformed other models in detecting fetal hypoxia, achieving high accuracy across pH, BDecf, Apgar1, Apgar5, and expert voting in all steps. It achieved over 98% accuracy across all objective criteria and steps. Full article

Even in the highest inhabited regions of the world, well above 2500 m altitude, women become pregnant and give birth to healthy children. The underlying adaptation to hypobaric hypoxia provides interesting insights into the physio(patho)logy of the human placenta. Although increasing altitude is regularly associated with fetal growth restriction (FGR), oxygen deficiency does not appear to be a direct cause. Rather, placental oxygen consumption is reduced to maintain the oxygen supply to the fetus. This comes at the expense of placental synthesis and transport functions, resulting in inappropriate nutrient supply. The hypoxia-inducible factor (HIF-1α), which modulates the mitochondrial electron transport chain to protect placental tissue from reactive oxygen species, plays a key role here. Reduced oxygen consumption also reflects decreased placental vascularization and perfusion, which is accompanied by an increased risk of maternal pre-eclampsia at high altitude. In native highlanders, the latter seems to be attenuated, partly due to a lower release of HIF-1α. In addition, metabolic peculiarities have been described in indigenous people that enhance glucose availability and thus reduce the extent of FGR. This review attempts to revisit the (albeit incomplete) knowledge in this area to draw the clinical reader’s attention to the crucial role of the placenta in defending the fetus against hypoxia. Full article

South American camelids inhabit high-altitude environments characterized by hypoxia, influencing embryonic, fetal, and placental development. This study examined the term placenta morphology of alpacas (Vicugna pacos, N = 12) and the immunoexpression of antioxidant selenoproteins (SP). We hypothesize that the placenta of alpacas, adapted to high altitudes, has characteristics with other species also adapted to altitude. Placentas were paraffin-embedded, sectioned (3–5 µm), stained with hematoxylin–eosin (H&E), Masson’s trichrome, and picrosirius red, and analyzed via light and polarized light microscopy. The chorion showed simple cuboidal epithelium with binucleated cells, a subepithelial mesenchyme rich in blood capillaries (area: 124.90 ± 9.82 µm²), and type III collagen fibers. The chorionic villi measured 2740.22 ± 132.75 µm. The allantois contained a simple columnar epithelium and mesenchyme with type I collagen fibers. Immunohistochemistry localized SP-N, SP-P, Dio-3, and GPx-3 in the blood capillaries and mesenchymal tissue of the chorion but not in the allantois. These findings were compared to human and sheep placentas from different altitudes due to a lack of camelid data at low levels. The morphological features resembled adaptations to hypoxia observed in other species. This preliminary study suggests a potential role for selenoproteins in hypoxia adaptation, providing a basis for future functional studies. Full article

Background/Objectives: A wide range of syphilis-related pregnancy complications are encountered in clinical practice. Active surveillance of the epidemiological situation in different countries and a series of retrospective data analyses allow for a comprehensive assessment of the feasible consequences of syphilis infection during pregnancy. The negative effects of infection on reproductive health are also described. Risk-increasing factors (inadequate or late treatment, partner coinfection) and protective factors (timely diagnostics and treatment) are distinguished. The importance of adequate and timely management as well as the accessibility of healthcare and socioeconomic status, which influence health outcomes, are stressed. This article presents a rare case of untreated syphilis infection during pregnancy. The infection was diagnosed during the first antenatal visit; how-ever, treatment was not initiated. At the 33rd week of gestation, the patient was admitted to the hospital because of sparse bloody vaginal discharge. Following sudden fetal hypoxia, an urgent cesarean section was performed at 33 weeks of gestation. A preterm newborn was delivered in critical condition, and congenital syphilis was diagnosed. Methods: We searched the PubMed, Cochrane, and MeSH databases using the key search terms “treponema pallidum”, “sexually transmitted infections”, “pregnancy”, “congenital infection”, “syphilis”, and “congenital syphilis”, as well as their combinations. A total of 28 papers published over a ten-year period were included in the literature review. A clinical case was analyzed. Results: The impact of syphilis on pregnancy is quite evident. Our case showcased one of the most common impacts, i.e., premature birth, of congenital infections with associated bacterial meningitis, respiratory distress syndrome, multiple organ damage, and insufficient weight. Such associations with many adverse pregnancy outcomes as well as congenital syphilis and neonatal defects are often avoidable. Conclusions: Considering the potential consequences of infections, the issue of sexually transmitted diseases remains relevant, and improving diagnostic and treatment opportunities becomes of paramount importance as cases increase. Full article

Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal–fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer’s disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis–trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau. We also highlighted the novel role of the Pin1-cis P-tau-ApoE axis in the development of preE, and propagation of cis P-tau-mediated abnormal protein aggregation (tauopathy) from the placenta to cerebral tissues later in life, leading to neurodegenerative conditions. In the case of preE, proteinopathy/tauopathy may interrupt trophoblast differentiation and induce cell death, similar to the events occurring in neurons. These events may eventually damage the endothelium and cause systemic features of disorders such as preE. Despite impressive research and therapeutic advances in both fields of preE and neurodegenerative diseases, further investigation of Pin1-cis P-tau and ApoE-related mechanistic underpinnings may unravel novel therapeutic options, and new transcriptional and proteomic markers. This review will also cover genetic polymorphisms in the ApoE alleles leading to dyslipidemia induction that may regulate the pathways causing preE or dementia-like features in the reproductive age or later in life, respectively. Full article