Search

Herein, eight common endocrine disrupting chemicals (EDCs) were exposed to zebrafish (Danio rerio) to investigate the relationship between different EDCs and their activated estrogen receptors. Under acute exposure, we identified five major malformation types whose incidence and deformity modes differed among EDCs. Luciferase analysis divided the EDC receptors into four categories: (i) triclosan (TCS), 17ß-estradiol (E2) and estriol (E3) mainly activated GPER expression; (ii) bisphenol A (BPA), p-(tert-octyl) phenol (POP), 17α-ethynylestradiol (EE2), E2 and E3 activated ERβ expression; (iii) E2 and E3 acted on both GPER and ERβ; and (iv) estrone (E1) and 9,9-bis(4-hydroxyphenyl)fluorene (BHPF) had little effect on the two receptors. In vivo immunofluorescence experiments on 96-hpf larvae provided evidence that TCS and POP acted on GPER and ERβ, respectively, while E2 acted on the two receptors simultaneously. Luciferase activities in the promoter regions of gper (-986 to -488) and erβ (-1998 to -1496) were higher than those in other regions, identifying these key regions as targets for transcription activity. TCS promoted GPER expression by acting on the JUND transcription factor, while POP promoted ERβ expression by activating the Foxl1 transcription factor. In contrast, E2 mainly regulated transcription of GPER and ERβ by Arid3a. These findings provide compelling evidence that different EDCs possess varying estrogen receptors, leading to differential regulatory pathways and abnormality symptoms. These results offer an experimental strategy and fundamental information to assess the molecular mechanisms of EDC-induced estrogen effects.

Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish (Danio rerio) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes (amhc, cmlc2, vmhc, and nkx2.5) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration. Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.

Aims/Introduction: To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin‐like growth factor‐1 (IGF‐1) and DPN in individuals with type 2 diabetes. Materials and Methods: A total of 790 patients with type 2 diabetes participated in a cross‐sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non‐DPN). Blood samples were taken to measure IGF‐1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing. Results: Patients with DPN exhibited significantly lower levels of IGF‐1 compared with non‐DPN patients (P < 0.001). IGF‐1 was positively correlated with the average amplitude of both motor (P < 0.05) and sensory nerves (P < 0.05), but negatively correlated with the vibration perception threshold (P < 0.05). No significant difference was observed between IGF‐1 and nerve conduction velocity (P > 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA1c, and the low levels of IGF‐1 as independent risk factors (P < 0.001). Receiver operating characteristic analysis determined that at 8 years duration of diabetes, 8.5% (69.4 mmol/mol) HbA1c and 120 ng/mL IGF‐1, the optimal cut‐off points, indicated DPN (P < 0.001). Conclusions: A reduction of IGF‐1 in patients with DPN suggests a potential protective role against axon injury in large fiber nerves of type 2 diabetes patients. [ABSTRACT FROM AUTHOR]