Figure - available from: Journal of Cachexia, Sarcopenia and Muscle
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DEHP/MEHP exposure increases proteolytic marker transcript expression and decreases the expression of myogenesis markers in mice and in C2C12 cells. (A) The relative levels of MuRF‐1, atrogin‐1/MAFbx, MyoD, and Myogenin mRNA transcripts in skeletal muscles of the offspring, determined by RT‐qPCR(n = 35 per group). (B) DEHP is metabolized into MEHP. (C) Treatment with 250 μM MEHP for 3 days reduced the viability and morphology of C2C12 cells. (D) MEHP treatment promoted C2C12 cell apoptosis (n = 3). (E) Western blot analyses revealed that MEHP treatment up‐regulated caspase‐3 cleavage and Myostatin expression in C2C12 cells in a dose‐dependent manner (n = 3). Data are representative images or expressed as the mean ± SD of each group from three separate experiments.*P < 0.05, **P < 0.0001 vs. the vehicle.
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Background:
Di-(2-ethylhexyl) phthalate (DEHP) and its metabolites can cross the placenta and may cause birth defects and developmental disorders. However, whether maternal DEHP exposure affects skeletal muscle development in the offspring and the pathways involved are unknown. This study investigated the effects of maternal DEHP exposure and the...
Citations
... The ubiquitin-proteasome pathway is primarily involved in skeletal muscle protein degradation [32]. MuRF-1 and atrogin-1 are skeletal muscle-specific ubiquitin ligases, whose activation induces the loss of muscle mass, that are used as markers of muscle atrophy [33]. DEX, a potent anti-inflammatory and immunosuppressive agent, is used for its biological effects. ...
Muscular atrophy is a chronic muscle disease characterized by a loss of muscle mass and muscle weakness due to excessive protein breakdown relative to protein synthesis. Apoptosis is a major factor in sarcopenia and the final stage of muscle atrophy that occurs via various mechanisms. In this study, we evaluated the protective effects of cell-free supernatants (CFSs) from different lactic acid bacteria (LAB) strains in dexamethasone (DEX)-treated C2C12 cells, followed by probiotic properties. We found that Limosilactobacillus fermentum (L. fermentum) MG4263 and MG5091 and Lactococcus lactis (Lc. lactis) MG4668 and MG5474 inhibited muscle atrophy F-box (atrogin-1) and muscle-specific RING-finger protein-1 (MuRF-1) in DEX-treated C2C12 cells. In addition, LAB strains inhibited the expression of apoptotic proteins, such as Bcl-2-associated X (Bax)/Bcl-2 and caspase-3 in DEX-treated C2C12 cells. L. fermentum MG5091, Lc. lactis MG4668, and MG5474 showed high survival rates in gastrointestinal (GIT) conditions and high adhesion rate to HT-29 cells. The LAB strains were also assessed for hemolysis and toxicity in HT-29 cells to confirm their stability. The LAB strains showed no hemolytic activity and toxicity to HT-29 cells. Therefore, L. fermentum MG5091, Lc. lactis MG4668, and MG5474 suggest their potential as probiotics to be used as functional foods for the inhibition of muscular atrophy.
Skeletal muscle plays a crucial role in maintaining metabolic function, energy homeostasis, movement function, as well as endocrine function. The gestation period is a critical stage for the myogenesis and development of skeletal muscle. Adverse environmental exposures during pregnancy would impose various effects on the skeletal muscle health of offspring. Maternal obesity during pregnancy can mediate lipid deposition in skeletal muscle of offspring by affecting fetal skeletal muscle metabolism and inflammation-related pathways. Poor dietary habits during pregnancy, such as high sugar and high fat intake, can affect the autophagy function of skeletal muscle mitochondria and reduce the quality of offspring skeletal muscle. Nutritional deficiencies during pregnancy can affect the development of offspring skeletal muscle through epigenetic modifications. Gestational diabetes may affect the function of offspring skeletal muscle by upregulating the levels of miR-15a and miR-15b in offspring. Exposure to environmental endocrine disruptors during pregnancy may impair skeletal muscle function by interfering with insulin receptor-related signaling pathways in offspring. This article reviews the research progress on effects and possible mechanisms of adverse maternal exposures during pregnancy on offspring skeletal muscle function in clinical and animal studies, aiming to provide scientific evidence for the prevention and treatment strategy of birth defects in skeletal muscle.
Corn oil, sodium carboxymethyl cellulose (CMC-Na), and dimethyl sulfoxide (DMSO) are widely used as solvents or suspensions in animal experiments, but the effects of prenatal exposure to them on fetal development have not been reported. In this study, Kunming mice were given a conventional dose of corn oil (9.2g/kg·d), CMC-Na (0.05g/kg·d) or DMSO (0.088g/kg·d) during gestation days 10-18, and the pregnancy outcome, fetal physical development, serum phenotype, and multi-organ function changes were observed. The results showed that corn oil decreased serum triglyceride level in males but increased their serum testosterone and CORT levels, and affected female placenta and female/male multi-organ functions (mainly bone, liver, kidney). CMC-Na increased female/male body lengths and tail lengths, decreased serum glucose and total cholesterol levels in males as well as increased their serum LDL-C/HDL-C ratio and testosterone level, decreased female serum bile acid level, and affected male/female placenta and multi-organ functions (mainly bone, liver, hippocampus). DMSO decreased male body weight and serum glucose level, decreased male/female serum bile acid levels, and affected male/female placenta and multi-organs functions (mainly bone, hippocampus, adrenal gland). In conclusion, prenatal exposure to a conventional dose of corn oil, CMC-Na or DMSO could affect fetal physical development and multi-organ functions, and has the characteristics of "multi-pathway, multi-organ and multi-target". This study provides the experimental basis for the rational selection of solvents or suspensions in pharmacology and toxicology studies. DATA AVAILABILITY: Data will be made available on request.
Due to the rising usage of plastics, plastic debris are present throughout marine ecosystems and detrimentally affects marine biota. Additionally, plastics likely result in elusive toxicity effects due to addition of plasticizers. The aim of the present study was to reveal the potential effects and mechanism of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP) and copollution of MPs and DEHP (MPs-DEHP) on Peneaus vannamei (P. vannamei) juveniles regarding oxidative stress, transcriptomics and metabolomics. MPs, DEHP and MPs-DEHP significantly induced the activities of superoxide dismutase (SOD) and catalase (CAT); MPs and DEHP have an antagonistic effect for malondialdehyde (MDA); suggesting that disorders of the antioxidant defence systems. 13, 133 and 58 differentially expressed genes and 21, 82 and 39 differentially expressed metabolites were responsible for the distinction of MPs, DEHP and MPs-DEHP groups, respectively. The combination of transcriptomic and metabolomic analyses showed that MPs, DEHP and MPs-DEHP exposure disturbed amino acid and lipid metabolism, and further induced inflammatory responses and dysfunction of purine metabolism. Furthermore, the presence of MPs might alleviate the biotoxicity of DEHP in P. vannamei. These findings provide new insights into the single and combined toxicological effects of MPs and additives for marine biota.
Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous environmental endocrine disruptor, is widely used in consumer products. Increasing evidence implies that DEHP influences the early development of the human brain. However, it lacks a suitable model to evaluate the neurotoxicity of DEHP. Using an established human cerebral organoid model, which reproduces the morphogenesis of the human cerebral cortex at the early stage, we demonstrated that DEHP exposure markedly suppressed cell proliferation and increased apoptosis, thus impairing the morphogenesis of the human cerebral cortex. It showed that DEHP exposure disrupted neurogenesis and neural progenitor migration, confirmed by scratch assay and cell migration assay in vitro. These effects might result from DEHP-induced dysplasia of the radial glia cells (RGs), the fibers of which provide the scaffolds for cell migration. RNA sequencing (RNA-seq) analysis of human cerebral organoids showed that DEHP-induced disorder in cell-extracellular matrix (ECM) interactions might play a pivotal role in the neurogenesis of human cerebral organoids. The present study provides direct evidence of neurodevelopmental toxicity of DEHP after prenatal exposure.
