PDF(Pubmed)
Abstract：
The plasticizer di (2-ethylhexyl) phthalate (DEHP) inhibits differentiation, impairs glucose metabolism, and decreases mitochondrial function in murine muscle satellite cells; however, if these effects are translated to human cells is unknown. The goal of this study was to evaluate changes in morphology and proliferation of primary human skeletal muscle cells exposed to DEHP. Rectus abdominis muscle samples were obtained from healthy women undergoing programed cesarean surgery. Skeletal muscle cells were isolated and grown under standard primary culture conditions, generating two independent sample groups of 25 subcultures each. Cells from the first group were exposed to 1 mM DEHP for 13 days and monitored for changes in cell morphology, satellite cell frequency and total cell abundance, while the second group remained untreated (control). Differences between treated and untreated groups were compared using generalized linear mixed models (GLMM). Cell membrane and nuclear envelope boundary alterations, loss of cell volume and presence of stress bodies were observed in DEHP-treated cultures. DEHP-treated cultures also showed a significant reduction in satellite cell frequency compared to controls. Exposure to DEHP reduced human skeletal muscle cell abundance. Statistical differences were found between the GLMM slopes, suggesting that exposure to DEHP reduced growth rate. These results suggest that exposure to DEHP inhibits human skeletal muscle cell proliferation, as evidenced by reduced cell abundance, potentially compromising long-term culture viability. Therefore, DEHP induces human skeletal muscle cell deterioration potentially inducing an inhibitory effect of myogenesis by depleting satellite cells.
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摘要：
增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）抑制分化，损害葡萄糖代谢，并降低小鼠肌肉卫星细胞的线粒体功能；然而，如果这些影响被转化为人类细胞是未知的。这项研究的目的是评估暴露于DEHP的原代人骨骼肌细胞的形态和增殖的变化。腹直肌样本是从接受有计划的剖宫产手术的健康女性中获得的。分离骨骼肌细胞并在标准原代培养条件下生长。生成两个独立的样本组，每组25个次培养。将来自第一组的细胞暴露于1mMDEHP13天，并监测细胞形态的变化，卫星细胞频率和总细胞丰度，而第二组保持未处理(对照)。使用广义线性混合模型(GLMM)比较处理组与未处理组之间的差异。细胞膜和核包膜边界改变，在DEHP处理的培养物中观察到细胞体积的损失和应激体的存在。与对照相比,DEHP处理的培养物还显示出卫星细胞频率的显著降低。暴露于DEHP降低了人骨骼肌细胞丰度。GLMM斜率之间存在统计差异，这表明暴露于DEHP会降低增长率。这些结果表明，暴露于DEHP抑制人骨骼肌细胞增殖，细胞丰度降低证明了这一点，可能损害长期文化生存能力。因此,DEHP诱导人骨骼肌细胞退化，可能通过消耗卫星细胞来诱导肌生成的抑制作用。
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