Bisphenol AF induces apoptosis via estrogen receptor beta (ERβ) and ROS-ASK1-JNK MAPK pathway in human granulosa cell line KGN. (1st February 2021)

• Record Type: Journal Article
• Authors: Huang, Mingquan; Li, Xingjie; Jia, Shengjun; Liu, Shuang; Fu, Li; Jiang, Xue; Yang, Meng
• Is Part Of: Environmental pollution. Volume 270(2021)
• Publication Date: 2021-02-01
• Subjects: Bisphenol AF -- Apoptosis -- Granulosa cells -- Estrogen receptor -- Oxidative stress; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.116051
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Bisphenol AF (BPAF) is an emerging environmental pollutant. Although BPAF is widely spread in the environment and human surroundings, its interference with ovarian function has not been fully elucidated. The aim of this study was to identify the mechanism underlying the effect of BPAF on the apoptosis of KGN cells, which maintain the physiological characteristics of ovarian granulosa cells. Our results indicated that BPAF induces KGN cell apoptosis in a concentration- and time-dependent manner. Meanwhile, BPAF exposure significantly promoted the expression of pro-apoptotic proteins, including Bax, Bid and Bak, while the expression of anti-apoptotic proteins, such as Bcl-2, Bcl-xL and Mcl-1, decreased significantly. We further detected a significant increase in intracellular ROS levels in response to high concentrations of BPAF exposure. After blocking the corresponding pathway, it was found that ROS mediates ASK1 and JNK activation. Furthermore, the role of Ca 2+ overload and estrogen receptor β (ERβ) in BPAF-induced KGN cell apoptosis was also confirmed by using inhibitors. These results suggest that BPAF has potential reproductive toxicity for females, and ROS-ASK1-JNK axis may play a key role in BPAF-induced ovarian dysfunction. In addition, Ca 2+ overload and ERβ pathway activation may also be an important mechanism of reproductive toxicity of BPAF. Graphical abstract: Image 1 Highlights: BPAF exposure induces KGN cell apoptosis in a concentration- and time-dependent manner. BPAF induces caspase activation and a decrease in mitochondrial membrane potential. BPAF exposure induces oxidative stress and calcium overload in KGN cells. BPAF-induced apoptosis is mediated by ROS-dependent activation of ASK1-JNK pathway. Calcium overload and estrogen receptor β mediates BPAF-induced apoptosis.