Khorsandi Layasadat, Heidari-Moghadam Abbas, Younesi Elham, Javad Khodayar Mohammad, Asadi-Fard Yousef
Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Int J Reprod Biomed. 2024 May 15;22(3):219-228. doi: 10.18502/ijrm.v22i3.16166. eCollection 2023 Mar.
Bisphenol A (BPA), an endocrine-disrupting agent, is widely used as polycarbonate plastics for producing food containers. BPA exposure at environmentally relevant concentrations can cause reproductive disorders.
The effect of Naringenin (NG) on BPA-induced Sertoli cell toxicity and its mechanism was examined in the present study.
In this experimental-laboratory study, the mouse TM4 cells were treated to BPA (0.8 μM) or NG for 24 hr at concentrations of 10, 20, and 50 μg/ml. Cell viability, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, antioxidant level, and mitochondrial membrane potential (MMP) were examined. The expression of mitophagy-related genes, including Parkin and PTEN-induced putative kinase 1 (Pink1), was also evaluated.
BPA significantly lowered the viability of the Sertoli cells (p= 0.004). Pink1 and Parkin levels of the BPA group were significantly increased (p 0.001), while the MMP was considerably decreased (p 0.001). BPA raised MDA and ROS levels (p 0.001) and reduced antioxidant biomarkers (p= 0.003). NG at the 20 and 50 μg/ml concentrations could significantly improve the viability and MMP of TM4 cells (p= 0.034). NG depending on concentration, could decrease Pink1 and Parkin at mRNA and protein levels compared to the BPA group (p = 0.024). NG enhanced antioxidant factors, while ROS and MDA levels were decreased in the BPA-exposed cells.
The beneficial impacts of NG on BPA-exposed Sertoli cells are related to the suppression of mitophagy and the reduction of oxidative stress.
双酚A（BPA）是一种内分泌干扰物，被广泛用作生产食品容器的聚碳酸酯塑料。在环境相关浓度下接触双酚A会导致生殖障碍。
本研究检测了柚皮素（NG）对双酚A诱导的支持细胞毒性的影响及其机制。
在本实验研究中，将小鼠TM4细胞用浓度为10、20和50μg/ml的双酚A（0.8μM）或柚皮素处理24小时。检测细胞活力、活性氧（ROS）产生、丙二醛（MDA）含量、抗氧化水平和线粒体膜电位（MMP）。还评估了包括帕金蛋白和PTEN诱导的假定激酶1（Pink1）在内的线粒体自噬相关基因的表达。
双酚A显著降低了支持细胞的活力（p = 0.004）。双酚A组的Pink1和帕金蛋白水平显著升高（p < 0.001），而线粒体膜电位则显著降低（p < 0.001）。双酚A提高了MDA和ROS水平（p < 0.001）并降低了抗氧化生物标志物（p = 0.003）。浓度为20和50μg/ml的柚皮素可显著提高TM4细胞的活力和线粒体膜电位（p = 0.034）。与双酚A组相比，柚皮素可根据浓度降低Pink1和帕金蛋白的mRNA和蛋白质水平（p = 0.024）。柚皮素增强了抗氧化因子，同时降低了双酚A处理细胞中的ROS和MDA水平。
柚皮素对双酚A处理的支持细胞的有益影响与线粒体自噬的抑制和氧化应激的降低有关。
