Search Results (26)

Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with chronic inflammation both in the placenta and systemically. PE is characterized by placental ischemia, which then results in the production and release of anti-angiogenic factors and inflammatory mediators. Inflammation in PE leads to placental, renal, and vascular damage, which contribute to the phenotype of hypertension and organ dysfunction during pregnancy. T cells, B cells, Natural Killer cells, and macrophages have all been shown to play a role in the inflammation present in the disease. T helper cells contribute to the chronic inflammation in PE. They also activate B cells, which produce agonistic autoantibodies against the angiotensin II type 1 receptor. Natural Killer cells are activated in PE and shift away from decidual Natural killer cells, which produce angiogenic factors, and toward cytotoxic Natural Killer cells, which contribute to tissue damage. Macrophages are polarized towards proinflammatory subtypes and contribute to tissue damage and inflammatory signaling in PE patients. As the immune system plays a role in the pathophysiology of the disease, it may be a potential target for therapeutic intervention to improve maternal and fetal outcomes during and following a PE pregnancy. Full article

Background: Endometriosis is a chronic inflammatory disorder that affects approximately 10% of women of reproductive age and exhibits tumor-like characteristics such as invasion, recurrence, and hormone-dependent proliferation despite its benign nature. Its pathogenesis is thought to involve hormonal imbalance, oxidative stress, hypoxia, immune dysregulation, and epigenetic alterations. This review summarizes how these factors contribute to lesion formation through intracellular signaling pathways, with a particular focus on the role of the stress-responsive transcription factor Forkhead box O (FOXO1). Methods: A comprehensive literature search was conducted using PubMed and Google Scholar without temporal restriction. Results: FOXO1 is a transcription factor that integratively regulates decidualization, cellular senescence, autophagy, and apoptosis. In the normal endometrium, under mild stress or hormonal stimulation, FOXO1 induces decidualization-associated genes (PRL, IGFBP1) and antioxidant enzymes, thereby promoting differentiation and survival. In contrast, in endometriosis, activation of the PI3K/AKT signaling pathway and an estrogen-dominant environment suppress the nuclear activity of FOXO1, leading to apoptosis resistance, accumulation of senescent cells, and chronic inflammation through the senescence-associated secretory phenotype (SASP). Moreover, depending on the intensity and duration of oxidative, metabolic, and environmental stress, FOXO1 drives distinct cellular fates—including decidualization, senescence, and apoptosis—thus contributing to the persistence and progression of endometriotic lesions. Conclusion: Dysregulation of the FOXO1-dependent cellular fate–control network plays a central role in the development of endometriosis. Elucidating the molecular mechanisms governing FOXO1 activity and its nuclear dynamics will be crucial for a comprehensive understanding of disease progression and for the development of novel therapeutic strategies. Full article

Objective: This study aimed to assess whether oocyte donation in triplet pregnancies is associated with increased risk of placental abnormalities and pregnancy complications compared to triplet pregnancies conceived through assisted reproductive technology (ART) without oocyte donation. Methods: This single-center, retrospective, case–control study analyzed triplet pregnancies conceived via ART. The case group included pregnancies resulting from oocyte donation, while the control group comprised triplet pregnancies conceived by ART without oocyte donation. Maternal, obstetric, fetal, and neonatal outcomes were assessed. Gross and histopathological placental findings were evaluated using standardized criteria. Univariate and multivariate statistical analyses were performed. Results: A total of 77 triplet pregnancies (231 fetuses) were included: 29 in the oocyte donation group (87 fetuses) and 48 in the non-oocyte donation group (144 fetuses). Multivariate analysis revealed significantly higher rates of pregnancy-induced hypertension (p = 0.03), preeclampsia (p = 0.03), fetal growth restriction (p = 0.04), and fetal death (p = 0.01) in the oocyte donation group. Placental evaluation showed a higher frequency of infarcts (p = 0.04) and chronic inflammatory lesions—chronic villitis (p = 0.02) and chronic deciduitis (p = 0.03)—as well as signs of fetal vascular malperfusion, including avascular villi (p = 0.02) and stromal–vascular karyorrhexis (p = 0.01). Intervillous fibrin deposition was also more common in this group (p = 0.02). Conclusions: Oocyte donation in triplet pregnancies is associated with increased rates of placental abnormalities and adverse maternal and fetal outcomes when compared with ART without oocyte donation. Placental examination may provide valuable insights into the mechanisms involved. Further research is warranted to clarify the underlying immunological and vascular pathways. Synopsis: In our cohort of 77 triplet pregnancies, those conceived via oocyte donation showed significantly higher rates of preeclampsia, fetal growth restriction, and fetal death. Placental examination revealed more chronic villitis, deciduitis, intervillous fibrin, avascular villi, and stromal–vascular karyorrhexis, suggesting immune and vascular dysfunction in oocyte donation pregnancies. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Introduction: In clinical practice, the presence of abnormal physiological root resorption frequently results in the retention of deciduous teeth. Also, unilateral mastication may contribute to the altered physiological process of root resorption. This delayed exfoliation and retention of deciduous teeth may compromise the integrity of adjacent soft tissue. In recent years, ozone therapy can be considered a promising strategy in accelerating healing and reducing pain in both traumatic and autoimmune ulcers. Case Presentation: This case report describes a 12 year-old male patient with localized damaged gingival tissue resulting from chronic trauma due to the retention of a deciduous tooth. Following the application of gaseous ozone therapy, complete mucosal healing was achieved. Conclusions: This case supports the potential of ozone therapy in paediatric soft tissue management. Full article

Endometriosis is a chronic disease characterized by the ectopic presence of endometrial cells that evade apoptosis and survive and proliferate under harsh environmental conditions. It is closely associated with infertility and pregnancy-related complications. This review focuses on the molecular pathophysiology of endometriosis, particularly the disruption of the p53–AMPK–mTOR signaling axis, and highlights the dysregulation of decidualization and cellular senescence, incorporating recent findings in reproductive physiology. A comprehensive literature search was conducted using PubMed and Google Scholar without temporal restrictions. Endometriotic cells adapt to the hostile peritoneal environment through resistance to apoptosis and alterations in autophagy. In the early stages, autophagy activation may promote cell survival; however, as the disease progresses, autophagic activity tends to decline. Aberrant activation of mTOR signaling is implicated in this process, contributing to the suppression of autophagy, impaired decidualization, and promotion of cellular senescence, ultimately facilitating lesion progression and infertility. Indeed, in the eutopic endometrium of patients with endometriosis, progesterone resistance, elevated inflammatory cytokines, and epigenetic abnormalities are known to reduce endometrial receptivity. Moreover, suppression of autophagy leads to excessive cellular senescence and secretion of the senescence-associated secretory phenotype (SASP), thereby interfering with proper decidualization. Maintaining an appropriate balance between decidualization and cellular senescence is essential for reproductive function. Future development of therapeutic strategies targeting these processes is expected to help overcome infertility associated with endometriosis. Full article

Persistent type I interferon (IFN-I) signaling compromises adaptive anti-HIV-1 T cell immunity and promotes viral reservoir persistence, yet its effects on innate lymphoid cells during chronic infection remain unclear. Through integrated single-cell RNA sequencing and functional validation in HIV-1-infected humanized mice with combination antiretroviral therapy (cART) and IFN-I signaling blockade, we reveal IFN-I-induced dysfunction of natural killer (NK) cells and group 3 innate lymphoid cells (ILC3s). Mechanistically, the IFN-I-CD9 axis drives NK cells toward a decidual NK cell-like phenotype, impairing their cytotoxic activity. Furthermore, IFNAR blockade rescues ILC3 functionality, which is critical for IL-17/IL-22-mediated antimicrobial defense and mucosal barrier maintenance. Our study delineates IFN-I-driven immunosuppression across innate lymphocyte compartments and proposes the targeted modulation of this pathway to enhance antiviral and mucosal immunity in HIV-1 management. Full article

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

Recurrent pregnancy loss (RPL) is a multifactorial condition affecting 1–5% of couples, often with unclear etiology. Idiopathic pregnancy losses (iPLs) are particularly challenging due to unknown molecular mechanisms. This study investigates the transcriptomic profiles of first-trimester products of conception (POC) from iPLs to uncover underlying molecular pathways. We performed RNA-sequencing on nine POC samples, identifying two distinct clusters enriched in trophoblast and decidual cells. Deconvolution analysis revealed reduced syncytiotrophoblast (STB) cells, with increased cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells in iPLs. Gene Set Enrichment Analysis highlighted immune pathways enrichment in both villous trophoblasts and decidua. Gene ontology (GO) analysis of downregulated genes implicated hormonal and endocrine processes, consistent with STB reduction, while upregulated genes were associated with MHC protein complex and immune system processes, aligning with EVT increases. Histological analysis showed chronic histiocytic intervillositis (CHI) in iPL samples, supporting maternal immune dysregulation in unexplained RPL. Together, transcriptomic and histological analyses indicate that immune signaling dysregulation and impaired trophoblast differentiation may underlie unexplained iPLs. These findings bridge molecular and histopathological evidence, underscoring the interplay between trophoblast dysfunction and immune imbalance. Our results provide insights into iPL pathogenesis, highlighting potential biomarkers that may contribute to improved diagnosis and future research. Full article

Deciduous teeth accumulate toxic metals until fully mineralized, making them a stable biological matrix for assessing chronic exposure during fetal and early postnatal life. Their metal content is influenced by environmental factors (e.g., industrial areas, mining sites) and individual factors (e.g., maternal diet, early nutrition, passive smoking). The aim of this study was to evaluate the toxic metal content in deciduous teeth and to identify factors contributing to its accumulation, as well as possible health implications. A systematic review was conducted in accordance with the PRISMA guidelines and following the PICO framework. Quality assessment was assessed using the Joanna Briggs Institute (JBI) checklist for quasi-experimental studies. The literature search was carried out in the PubMed, Scopus, and Web of Science databases using the following keywords: deciduous, milk, primary, decidua, teeth, dentition, heavy metal, toxic metals. A total of 134 articles were initially identified, with 95 remaining after duplicate removal. After screening, 75 articles were excluded: 71 did not meet the inclusion criteria, 3 were not available in English, and 1 lacked full-text access. Ultimately, 20 studies were included in the review. Toxic metal concentrations were determined using various analytical techniques, mainly inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS). Higher levels of metals, especially lead, were observed in the teeth of children residing in industrial areas, near mines, or in regions affected by armed conflict. Although two out of five studies indicated a possible link between fathers’ smoking habits and elevated lead concentrations, no definitive relationship was established between secondhand smoke exposure and the levels of lead and cadmium found in dental tissue. Similarly, no definitive relationship was identified between mercury and lead content and the prevalence of autism. However, lower manganese levels were associated with the presence of autistic traits, weaker verbal performance, and reduced memory capacity. In conclusion, deciduous teeth represent a valuable biological material for assessing chronic prenatal and early postnatal exposure to toxic metals, which may serve as a starting point for further research into diseases of unknown etiology, such as autism, and in the future may have clinical significance in their prevention and treatment. And it is also important for monitoring environmental pollution levels. Full article

Endometriosis is a chronic gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. A common feature of this pathology is the impaired decidualization of endometrial stromal cells, a critical process that prepares the uterus for embryo implantation. This decidualization defect has been mechanistically linked to progesterone resistance in endometriotic lesions. However, the presence and underlying mechanisms of decidualization defects in the eutopic endometrium of women with endometriosis remain controversial. The aim of the present study is to integrate and discuss molecular evidence from both in vivo and in vitro studies examining decidualization alterations in the eutopic endometrium of patients with endometriosis. Multiple studies have demonstrated impaired decidualization in the eutopic endometrium of women with endometriosis. These alterations have been reported on multiple genes, signaling pathways, and epigenetic processes. However, additional functional studies are warranted to elucidate whether these decidualization defects directly contribute to endometriosis-associated infertility. A better understanding of the decidualization process and its dysregulation in endometriosis will not only advance the development of targeted fertility treatments but also facilitate the design of more effective therapeutic strategies for managing this chronic condition. Full article

Background: There is a high rate of depressive symptoms such as irritability, anhedonia, fatigue, and hypersomnia in patients with type 2 diabetes mellitus (T2DM). However, the causes and underlying mechanisms of the comorbidity of depression and diabetes remain unknown. Methods: For the first time, we identified Decidual protein induced by progesterone 1 (Depp1), also known as DEPP autophagy regulator 1, as a hub gene in both depression and T2DM models. Depp1 levels were increased in the mPFC but not in other brain regions, such as the hippocampus or nucleus accumbens, according to Western blot and PCR assays. Results: Glucose dysregulation and synaptic loss occur in both depression and T2DM. The typical hyperglycemia in T2DM was observed in two models of depression, namely, chronic social defeat stress (CSDS) and chronic restraint stress (CRS). Hyperglycemia, which occurred in T2DM, was observed, and metabolomics data clearly showed the perturbation of glucose levels and glucose metabolism in the medial prefrontal cortex (mPFC). Decreased protein levels of BDNF and PSD95 suggested significant synaptic loss in depressed and diabetic mice. Conclusion: These findings suggest that the comorbidity of depression and diabetes is involved in the dysfunction of Depp1 in the mPFC. Full article

This narrative review evaluates the literature on the management of mandibular condyle fractures in growing patients. It aims to illustrate some fundamental biological principles and to offer a series of considerations applicable to clinical practice. The discussion is based on 116 papers published in PubMed and two relevant textbooks. Condylar fractures may be overlooked, especially in pre-scholar children, where compliance is usually reduced. However, these injuries can have disabling sequelae such as ankyloses, facial deformities, malocclusion, and chronic pain in some patients if not diagnosed and managed correctly. Due to their significance, mandibular condyle fractures in children are a subject of considerable clinical interest. As of today, there is consensus about their treatment. Four management options are available: expectative (analgesia, soft food and follow-up), functional protocols (guiding elastics, orthodontic appliances and exercises), maxillomandibular fixation (MMF), and open reduction and internal fixation (ORIF). Nondisplaced and minimally displaced fractures should be treated expectantly; severely displaced non-comminuted fractures can be safely operated on if the expertise is available, even in patients with deciduous dentition. Moderately displaced fractures can be managed with functional protocols or operatively, depending on the background and know-how of the specialist. Functional protocols can achieve good outcomes, especially in patients with deciduous dentition. MMF should be foregone in children due to its many drawbacks. Full article

Background: A healthy pregnancy begins with an adequate endometrial state, even before the arrival of a blastocyst. Proper endometrial priming and the development of a tolerogenic decidua are key steps in creating the perfect environment for implantation and pregnancy. In these processes, the involvement of the maternal immune system seems to be of great relevance, modulating the different decidual immune populations to prepare the endometrium for a potential pregnancy. However, certain local pathologies of an inflammatory and autoimmune nature appear to have a direct impact on these phenomena, thus altering patients’ reproductive outcomes. Methods: This literature review analyzes original articles, reviews, systematic reviews, and meta-analyses published between 1990 and 2024, concerning the impact of different inflammatory and autoimmune conditions on endometrial status and fertility. The included papers were obtained from Medline (Pubmed) and the Cochrane library. Results: There is evidence that endometriosis, adenomyosis, and chronic endometritis, through the promotion of a chronic inflammatory environment, are capable of altering endometrial immune populations, and, thus, processes essential for early pregnancy. Among other effects, these conditions have been linked to impaired decidualization, alterations in progesterone responsiveness, and hindered placentation. Similarly, antiphospholipid syndrome (APS), thyroid dysfunction, diabetes, and other pathologies related to glucose and gluten metabolism, due to their autoimmune nature, also appear to have a local impact on the uterine environment, affecting reproductive success through different mechanisms, including altered hormonal response and, again, impaired decidualization. Conclusions: The management of inflammatory and autoimmune diseases in assisted reproduction patients is gaining importance due to their direct impact on the endometrium. It is necessary to follow current expert recommendations and established therapeutic approaches in order to improve patients’ prospects, ranging from antibiotic treatment in chronic endometritis to heparin and aspirin in APS, as well as hormonal treatments for endometriosis/adenomyosis or a gluten-free diet in celiac disease. All of them and the rest of the therapeutic perspectives, both current and under investigation, are presented throughout this work, assessing the possible improvements for reproductive outcomes. Full article