Search Results (101)

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

Bisphenols (BPs), particularly bisphenol A (BPA) and its structural analogues, are synthetic compounds widely used in plastics and industrial materials. These substances are also recognised as endocrine-disrupting chemicals (EDCs) due to their ability to interfere with hormonal systems, which has significant implications for aquatic organisms. This review summarises the occurrence, environmental distribution, and toxicity of BPs in fish, with a focus on estrogenic, androgenic, thyroid, and glucocorticoid disruptions. Studies consistently show that exposure to BPs leads to altered gene expression, developmental abnormalities, impaired reproduction, and disrupted hormonal signalling in various fish species. Although BPA alternatives like bisphenol S, bisphenol F, or bisphenol AF were introduced as safer options, emerging evidence suggests they may pose equal or greater risks. Regulatory measures are evolving, particularly within the European Union, but legislation remains limited for many bisphenol analogues. This review emphasises the need for comprehensive environmental monitoring, stricter regulatory frameworks, and the development of genuinely safer alternatives to minimise the ecological and health impacts of BPs in aquatic systems. Full article

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article

Plastic overconsumption has emerged as a major environmental pollutant, with degraded micro- and nanoplastic (MNP) particles being consumed by a vast variety of species. MNPs, particles < 5 mm, contain endocrine-disrupting chemicals (EDCs), which can bind to hormone receptors and disrupt the proper endocrinological function of a variety of organs. This review explores the toxicological impact of MNPs on the hypothalamus, pituitary gland, thyroid, pineal body, ovaries, and testes, as well as the effects of the endocrinological regulatory axes, including the hypothalamic–pituitary–gonadal (HPG), hypothalamic–pituitary–thyroid (HPT), and hypothalamic–pituitary–adrenal (HPA) axes. The disruption of these hormonal feedback systems leads to reproductive dysfunction, neurotoxicity, cytotoxicity, immunotoxicity, and metabolic disorders. The gonads are particularly susceptible, with studies demonstrating oxidative stress, cellular apoptosis, and infertility due to MNP exposure. Given the widespread presence of MNPs and their impact on human health, further research is critical to understand their long-term effects and develop strategies to reduce exposure. Full article

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic review aims to evaluate the current epidemiological evidence linking EDC exposure with adverse reproductive outcomes in males and females of reproductive age. A total of 14 observational studies published between 2014 and 2024 were included following structured searches in PubMed, Scopus, and Google Scholar. The most commonly studied EDCs included bisphenol A (BPA), its analogs (such as bisphenol S, BPS), phthalates, parabens, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs). The review found consistent associations between EDC exposure and multiple reproductive endpoints, such as impaired semen quality, decreased ovarian reserve, infertility, polycystic ovary syndrome (PCOS), altered hormone levels—specifically estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—and adverse outcomes in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Despite methodological heterogeneity, the findings support the biological plausibility of EDCs in disrupting reproductive function. The review highlights the urgent need for regulatory measures, increased public awareness, and longitudinal studies to assess the cumulative effects of chronic EDC exposure on human fertility. Full article

Micronutrients and environmental factors are key exogenous agents influencing thyroid DNA integrity. Micronutrients act as cofactors in DNA replication, repair, and antioxidant defence, while environmental exposure, such as radiation, heavy metals, and endocrine-disrupting chemicals, can directly damage DNA, leading to genomic instability. Although many studies have confirmed the link between micronutrient status and thyroid health, the effects of nutrient imbalances and environmental stressors on thyroid DNA remain underexplored. This narrative review examines how these factors may compromise thyroid genome stability and contribute to disease development. The analysis focused on the roles of iodine, selenium, iron, zinc, copper and vitamins D, B9, and B12 as well as environmental exposures such as radiation, heavy metals, and endocrine-disrupting chemicals. The findings suggest that both micronutrient imbalance and environmental stress can impair DNA integrity in thyroid cells. Understanding these complex relationships is critical for developing effective strategies to maintain thyroid health and mitigate the risk of thyroid diseases associated with compromised genomic integrity. Methodology: This narrative review was based on 254 articles retrieved through a manual search of the PubMed and Google Scholar databases, covering the years 2000–2025 and focusing on the influence of micronutrients and environmental factors on thyroid DNA integrity and repair. Several seminal earlier publications, fundamental to a comprehensive understanding of the topic, were also included. Full article

Bifenthrin (BF) is a widely used pyrethroid pesticide recognized as an endocrine-disrupting chemical (EDC). Previous studies have confirmed that chronic exposure to BF is associated with various health risks. However, its potential association with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) remains unclear. In this study, the potential targets of BF were identified using several databases, including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH. Differentially expressed genes (DEGs) associated with RIF were obtained from bulk RNA-seq datasets in the GEO database. Candidate targets were identified by intersecting the predicted BF-related targets with the RIF-associated DEGs, followed by functional enrichment analysis using the DAVID and g:Profiler platforms. Subsequently, hub genes were identified based on the STRING database and Cytoscape. A diagnostic model was then constructed based on these hub genes in the RIF cohort and validated in an independent recurrent pregnancy loss (RPL) cohort. Additionally, we performed single-cell type distribution analysis and immune infiltration profiling based on single-cell RNA-seq and bulk RNA-seq data, respectively. Molecular docking analysis using AutoDock Vina was conducted to evaluate the binding affinity between BF and the four hub proteins, as well as several hormone-related receptors. Functional enrichment results indicated that the candidate genes were mainly involved in apoptotic and oxidative stress-related pathways. Ultimately, four hub genes—BCL2, HMOX1, CYCS, and PTGS2—were identified. The diagnostic model based on these genes exhibited good predictive performance in the RIF cohort and was successfully validated in the RPL cohort. Single-cell transcriptomic analysis revealed a significant increase in the proportion of myeloid cells in RPL patients, while immune infiltration analysis showed a consistent downregulation of M2 macrophages in both RIF and RPL. Moreover, molecular docking analysis revealed that BF exhibited high binding affinity to all four hub proteins and demonstrated strong binding potential with multiple hormone receptors, particularly pregnane X receptor (PXR), estrogen receptor α (ESRα), and thyroid hormone receptors (TR). In conclusion, the association of BF with four hub genes and multiple hormone receptors suggests a potential link to immune and endocrine dysregulation observed in RIF and RPL. However, in vivo and in vitro experimental evidence is currently lacking, and further studies are needed to elucidate the mechanisms by which BF may contribute to RIF and RPL. Full article

The prenatal environment critically influences sow and offspring health, with the liver being highly susceptible to heat stress (HS) and vital for antioxidant defense. However, mechanisms underlying HS impacts on early pregnancy and hepatic adaptation remain unclear. This study applied multi-omics to analyze chronic HS responses in early-pregnancy sows. Results demonstrated that HS reduced blood oxygen (PO₂) and basophils while elevating red blood cell parameters (RBC, HGB, and HCT). Endocrine disruptions included upregulated adrenal hormones (ACTH and cortisol) and suppressed thyroid (T3 and TSH) and reproductive hormones (LH1 and FSH). Liver dysfunction was evident through elevated biomarkers (AST, ALT, and TBIL) and pro-inflammatory IL-6, coupled with reduced anti-inflammatory IL-10. HS induced oxidative stress, marked by increased total antioxidant capacity (T-AOC) but decreased SOD and MDA levels. Liver tissue exhibited apoptosis (Bax/CD8 upregulated and Bcl-2 downregulated) and upregulated heat shock proteins (HSP70/90). Multi-omics analysis demonstrated that under heat stress conditions, the pyrimidine metabolism, oxidative phosphorylation, and tryptophan metabolism pathways were significantly upregulated in the liver. This upregulation may be mediated by key metabolites, including AMP, NAD, and UMP. These metabolites likely contribute to the body’s adaptation to heat stress. Chronic HS impaired liver function and anti-inflammatory responses but triggered compensatory antioxidant and metabolic reprogramming. These findings underscore the liver’s dual characteristics of vulnerability and resilience under high-temperature stress, offering valuable mechanistic insights that can inform strategies to enhance heat tolerance in pregnant sows. Full article

Mpox (MPX), caused by the Monkeypox virus (MPXV), is a zoonotic orthopoxvirus infection with increasing global relevance due to sustained human-to-human transmission. While primarily known for cutaneous and systemic involvement, emerging evidence suggests that MPX may also disrupt endocrine function. This narrative review aims to synthesize current clinical, experimental, and epidemiological findings on MPX-related endocrine complications. We explore the potential impact of MPXV on the thyroid, adrenal glands, and gonads, and discuss the underlying mechanisms, clinical manifestations, and implications for patient management. MPX has been implicated in viral-induced subacute thyroiditis, with cases exhibiting thyrotoxicosis followed by hypothyroidism, likely mediated by direct viral infiltration or immune dysregulation. Additionally, MPX may contribute to adrenal insufficiency through viral invasion, immune-mediated destruction, or hypothalamic–pituitary–adrenal (HPA) axis dysfunction, exacerbating metabolic and inflammatory complications. MPXV’s persistence in testicular tissue raises concerns about reproductive health, with potential implications for fertility, hormone production, and viral transmission. The virus may also modulate host steroid pathways through interactions with glucocorticoid, androgen, and estrogen receptors, influencing immune responses and disease severity. Given these findings, clinicians should maintain vigilance for endocrine dysfunction in MPX patients, particularly in immunocompromised individuals. The role of steroid therapy in MPX remains complex, requiring careful balancing of its anti-inflammatory benefits against potential risks of viral persistence and immune suppression. Further research is essential to clarify MPX’s endocrine impact and optimize management strategies. Full article

Reserpine is used as a cheap and effective first-line antihypertensive, and presently, it is applied as treatment for difficult-to-control cases of hypertension. Despite its significance, reserpine’s neuroendocrine toxicity remains largely underexplored. Here, we investigated the effects of reserpine on development, locomotion, central nervous system (CNS) neurons, thyroid development, and the expression of genes related to neurodevelopment, endocrine, learning and memory, and depression in zebrafish exposed to different doses of reserpine ranging from 0.5 mg/L to 16 mg/L. The results of our study demonstrated that reserpine exerts dose-dependent toxicity on the neuroendocrine system (NES). An investigation into its underlying mechanism suggests that reserpine disrupted the hypothalamic–pituitary–thyroid (HPT) axis via down-regulating hhex, tg, and tshβ genes, impairing thyroid hormone synthesis and endocrine balance. Meanwhile, it affected neurodevelopment, as evidenced by the reduced expression of gfap, gap43, mbp, syn2a, and tuba1b genes, which compromised neuronal structure and function, while impaired neurotransmitter release and uptake could occur due to the suppression of crhb and mao genes. To conclude, these findings illustrate the interconnected impact of pathways involved in endocrine and neurodevelopment in reserpine-induced toxicity. Full article

Thyroid hormones (THs) play a crucial role in various biological functions, including metabolism, cell growth, and nervous system development, and any alteration involving the structure of the thyroid gland and TH secretion may result in thyroid disease. Growing evidence suggests that phthalate plasticizers, which are commonly used in a wide range of products (e.g., food packaging materials, children’s toys, cosmetics, medical devices), can impact thyroid function, primarily affecting serum levels of THs and TH-related gene expression. Like phthalate compounds, recently introduced alternative plasticizers can leach from their source material into the environment, particularly into foods, although so far only a very limited number of studies have investigated their thyroid toxicity. This review aimed at summarizing the current knowledge on the role of phthalate and non-phthalate plasticizers in thyroid dysfunction and disease, describing the major biological mechanisms underlying this relationship. We will also focus on the food industry as one of the main players for the massive spread of such compounds in the human body, in turn conveyed by edible compounds. Given the increasing worldwide use of plasticizers and the essential role of THs in humans, novel strategies should be envisaged to reduce this burden on the thyroid and, in general, on human health. Full article

The prevalence of hyperthyroidism in cats has been steadily increasing worldwide since the late 1970s. The main cause of feline hyperthyroidism remains unknown. The underlying cause was studied from the viewpoint of the “One Health” concept, which is an approach integrating environmental, animal and human health. Looking at the dietary difference between cats which are carnivores and dogs which appear to be omnivores like humans, there is a possibility that cats take in a comparatively greater amount of endocrine-disrupting chemicals such as polybrominated diphenyl ethers (PBDEs) than dogs and humans via the fish-based food web. PBDEs have been used worldwide as flame retardants since the 1970s. It is considered that PBDEs mimic thyroid-stimulating hormones to cause a thyroid adenoma, which is often active and produces excessive thyroid hormones, resulting in symptomatic hyperthyroidism. The increasing prevalence of feline hyperthyroidism may be associated with Minamata disease that was caused by methyl-mercury contamination in the 1950s. This environmental contamination firstly wreaked havoc as neurological disorders in local cats, and this occurrence was a sign that severe neurological disorders would next develop in large numbers of local people. The prevalence of feline hyperthyroidism may be a sign of what will next emerge in human beings. Full article

Water environments contaminated with arsenic (As) have become a significant environmental concern. Previous research has highlighted the detrimental effects of As on fish, but limited knowledge exists regarding its impacts on endocrine systems. To address this gap, zebrafish embryos were exposed to various concentrations (0, 25, 50, 75, and 150 μg/L) of arsenate (AsV) for 120 h post-fertilization (hpf). Our findings indicate that exposure to AsV significantly increases cortisol- and thyroid-stimulating hormone (TSH) levels while decreasing estradiol (E2) and testosterone (T) levels. Additionally, it initially decreases and then increases thyroxine (T4) contents. Furthermore, several key genes relevant to these endocrine systems also show significant influences. The results from principal component analysis demonstrate that TRH, TSH, TRHRb, and TRβ primarily affect the level of T4 while Cyp11b, StAR, hmgrb MC2R, and GR mainly influence cortisol levels. On the other hand, Cyp19a, Cyp17, 17βhsd, ERβ, LHR, hmgrb, and AR predominantly impact E2 and T levels. Transcriptomics and enrichment analysis reveal that these pathways are primarily associated with steroid hormone synthesis and transport. Furthermore, it was found that AsV stimulates the cAMP signaling pathway through a compensation mechanism. These results suggest that AsV may potentially act as environmental endocrine-disrupting chemicals with non-negligible interference effects on the endocrine system in zebrafish. This study holds theoretical value in assessing the environmental risk posed by As overall as well as providing an important basis for addressing human health issues and implementing preventive measures. Full article

The thyroid gland is an endocrine organ whose hormones enable the proper functioning of the organism. The normal function of this organ is influenced by internal and external factors. One of the external factors is trace elements. Trace elements in appropriate concentrations are necessary for the proper functioning of the thyroid. Fe, Cu, Mn, I, Zn, and Se are part of the enzymes involved in oxidative stress reduction, while Cd, Hg, and Pb can increase ROS production. Cu and Fe are necessary for the correct TPO synthesis. An imbalance in the concentration of trace elements such as Fe, Cu, Co, I, Mn, Zn, Ag, Cd, Hg, Pb, and Se in thyroid cells can lead to thyroid diseases such as Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism, autoimmune thyroiditis, thyroid nodules, thyroid cancer, and postpartum thyroiditis. Lack of adequate Fe levels may lead to hypothyroidism and cancer development. The thyroid gland’s ability to absorb I is reversibly reduced by Co. Adequate levels of I are required for correct thyroid function; both deficiency and excess can predispose to the development of thyroid disorders. High concentrations of Mn may lead to hypothyroidism. Furthermore, Mn may cause cancer development and progression. Insufficient Zn supplementation causes hypothyroidism and thyroid nodule development. Cd affecting molecular mechanisms may also lead to thyroid disorders. Hg accumulating in the thyroid may interfere with hormone secretion and stimulate cancer cell proliferation. A higher risk of thyroid nodules, cancer, autoimmune thyroiditis, and hypothyroidism were linked to elevated Pb levels. Se deficiency disrupts thyroid cell function and may lead to several thyroid disorders. On the other hand, some of the trace elements may be useful in the treatment of thyroid diseases. Therefore, the effects of trace elements on the thyroid require further research. Full article

Bisphenol A (BPA) is a prevalent environmental contaminant found in plastics and known for its endocrine-disrupting properties, posing risks to both human health and the environment. Despite its widespread presence, the impact of BPA on papillary thyroid cancer (PTC) progression, especially under realistic environmental conditions, is not well understood. This study examined the effects of BPA on PTC using a 3D thyroid papillary tumor spheroid model, which better mimicked the complex interactions within human tissues compared to traditional 2D models. Our findings demonstrated that BPA, at environmentally relevant concentrations, could induce significant changes in PTC cells, including a decrease in E-cadherin expression, an increase in vimentin expression, and reduced thyroglobulin (TG) secretion. These changes suggest that BPA exposure may promote epithelial–mesenchymal transition (EMT), enhance invasiveness, and reduce cell differentiation, potentially complicating treatment, including by increasing resistance to radioiodine therapy. This research highlights BPA’s hazardous nature as an environmental contaminant and emphasizes the need for advanced in vitro models, like 3D tumor spheroids, to better assess the risks posed by such chemicals. It provides valuable insights into the environmental implications of BPA and its role in thyroid cancer progression, enhancing our understanding of endocrine-disrupting chemicals. Full article