Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Chemosphere. 2020 Dec;261:127693. doi: 10.1016/j.chemosphere.2020.127693. Epub 2020 Jul 23.
Nonylphenol (NP) is a kind of environmental endocrine disruptors which is generally recognized to cause female reproductive toxicity, but its basic mechanism has not been fully elucidated. In this study, granulosa cells (GCs) were treated with 0-70 μM NP for 24 h, the cell viability of GCs was reduced significantly, as well as increased cell apoptosis with G2/M arrest. Furthermore, NP significantly induced autophagy and the production of reactive oxygen species (ROS). However, these phenomenons were inhibited by blocking the production of ROS with N-Acetyl-l-cysteine (NAC) administration. Intriguingly, the inhibition of autophagy with 3-Methyladenine (3-MA) could enhance the apoptosis induced by NP. Moreover, the down regulating of p-Akt/Akt, p-mTOR/mTOR and subsequent up-regulation of p-AMPK/AMPK induced by NP can be rescued by pretreatment of NAC. Our findings suggested that NP promotes rat ovarian GCs apoptosis and autophagy simultaneously, which may involve the activation of ROS-dependent Akt/AMPK/mTOR pathway. Whatever, the activation of autophagy is likely to develop a protective mechanism to improve the apoptosis of rat ovarian GCs induced by NP.
壬基酚（NP）是一种环境内分泌干扰物，普遍认为其会导致雌性生殖毒性，但基本机制尚未完全阐明。在这项研究中，将颗粒细胞（GCs）用 0-70μM 的 NP 处理 24 小时，GCs 的细胞活力明显降低，同时 G2/M 期阻滞导致细胞凋亡增加。此外，NP 还显著诱导自噬和活性氧（ROS）的产生。然而，用 N-乙酰半胱氨酸（NAC）抑制 ROS 的产生可以抑制这些现象。有趣的是，用 3-甲基腺嘌呤（3-MA）抑制自噬可以增强 NP 诱导的凋亡。此外，NP 诱导的 p-Akt/Akt、p-mTOR/mTOR 下调和随后的 p-AMPK/AMPK 上调可以被 NAC 的预处理挽救。我们的研究结果表明，NP 同时促进大鼠卵巢 GCs 凋亡和自噬，这可能涉及 ROS 依赖性 Akt/AMPK/mTOR 通路的激活。无论如何，自噬的激活可能会形成一种保护机制，以改善 NP 诱导的大鼠卵巢 GCs 的凋亡。
