Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, Jilin 130000, China; The Second Hospital of Dalian Medical University, Dalian, Liaoning 116012, China.
Department of Preventive Medicine, School of Public Health, Jilin University, Changchun, Jilin 130000, China; Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, Jilin 130000, China.
Environ Toxicol Pharmacol. 2015 Mar;39(2):643-50. doi: 10.1016/j.etap.2015.01.005. Epub 2015 Jan 20.
Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is considered to be a reproductive toxicant. This study was performed to evaluate the effect of MEHP on apoptosis of rat ovarian granulosa cells and explore potential mechanism. Granulosa cells were treated with MEHP (0, 25, 50, and 100 μmol/l). Inhibited cell viability and increased apoptosis rate were observed in 50 and 100 μmol/l groups. CASPASE3 activity and BAX expression were significantly raised in all MEHP-treated groups; BCL2 expression was elevated in 25 μmol/l group, while inhibited in 50 and 100 μmol/l groups; BAX/BCL2 ratio was increased in a typical dose-effect relationship. In conclusion, this study showed that MEHP exposure induced cell viability decrease and apoptosis, associated with increase of CASPASE3 activity and BAX/BCL2 ratio. Moreover, CASPASE3 activity showed a reversed dose-dependent effect in MEHP-treated groups, indicating there might exist other CASPASE-independent pathway involved in MEHP-induced apoptosis.
邻苯二甲酸二(2-乙基己基)酯(DEHP)的代谢产物单(2-乙基己基)邻苯二甲酸酯(MEHP)被认为是一种生殖毒性物质。本研究旨在评估 MEHP 对大鼠卵巢颗粒细胞凋亡的影响,并探讨其潜在机制。用 MEHP(0、25、50 和 100μmol/L)处理颗粒细胞。在 50 和 100μmol/L 组观察到细胞活力受到抑制,凋亡率增加。所有 MEHP 处理组的 CASPASE3 活性和 BAX 表达均显著升高;在 25μmol/L 组 BCL2 表达升高,而在 50 和 100μmol/L 组则受到抑制;BAX/BCL2 比值呈典型的剂量效应关系增加。综上所述,本研究表明,MEHP 暴露诱导细胞活力下降和凋亡,与 CASPASE3 活性和 BAX/BCL2 比值增加有关。此外,MEHP 处理组中 CASPASE3 活性呈反向剂量依赖性,表明 MEHP 诱导的细胞凋亡可能存在其他不依赖 CASPASE 的途径。