Mitochondrial respiratory chain complex abnormal expressions and fusion disorder are involved in fluoride-induced mitochondrial dysfunction in ovarian granulosa cells. (January 2019)

• Record Type: Journal Article
• Authors: Zhao, Wen-peng; Wang, Hong-wei; Liu, Jing; Zhang, Zi-hao; Zhu, Shi-quan; Zhou, Bian-hua
• Is Part Of: Chemosphere. Volume 215(2019)
• Page Start: 619
• Page End: 625
• Publication Date: 2019-01
• Subjects: Fluoride -- Mitochondria -- Mitochondrial respiratory chain complex -- Mitochondrial fusion protein -- Granulosa cells; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2018.10.043
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Excessive fluoride intake has a strong female reproductive toxicity, which can result in follicular developmental dysplasia and decrease oocytes developmental potential. The underlying mechanisms of fluoride-induced mitochondrial dysfunction in ovarian granulosa cells remain largely unknown. In this study, the ultrastructure changes of mitochondria and DNA damage in ovarian granulosa cells were observed under transmission electron microscope and TUNEL staining. Then, the ATP content and ROS level in granulosa cells were measured. The expression of mitochondrial fusion proteins and mitochondrial respiratory chain complexes, including OPA1 and Mfn1, and NDUFV2, SDHA and CYC1, in the ovarian tissues were measured by immunohistochemistry, Western blot and Quantitative real-time PCR analyses. The expression of ATP5j and ATP5h in the ovarian tissues was also measured. Results show that fluoride treatment considerably damages mitochondrial ultrastructure and enhances the apoptosis of granulosa cells. The ATP content greatly decreased, whereas the ROS level increased after fluoride treatment. The expression level of Mfn1 in the ovarian tissue was up-regulated, whereas OPA1 expression had no significant change. The expression levels of NDUFV2, SDHA and CYC1 were considerably up-regulated, and the expression of ATP5j and ATP5h were down-regulated after fluoride treatment. In summary, the damage in the mitochondrial ultrastructure, ATP content decrease, ROS level increase and the abnormal expression of OPA1, Mfn1, NDUFV2, SDHA, CYC1, ATP5j and ATP5h in ovary tissue are closely associated with fluoride-induced mitochondrial dysfunction, which might be responsible for the follicular developmental dysplasia and the potential decrease in oocyte development induced by fluoride in female mice. Highlights: Fluoride damaged mitochondrial ultrastructure in ovarian granulosa cells. Fluoride induced mitochondrial fusion disorder. Fluoride interfered with the expression of mitochondrial respiratory chain complex. Fluoride decreased ATP content and increased ROS levels. Fluoride induced mitochondrial dysfunction in ovarian granulosa cells.