Mitochondrial respiratory chain complex abnormal expressions and fusion disorder are involved in fluoride-induced mitochondrial dysfunction in ovarian granulosa cells
| Autor: | Bian-hua Zhou, Shi-quan Zhu, Jing Liu, Hong-wei Wang, Wen-peng Zhao, Zi-hao Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
endocrine system
Environmental Engineering Health Toxicology and Mutagenesis 0208 environmental biotechnology SDHA Ovary 02 engineering and technology 010501 environmental sciences Mitochondrion 01 natural sciences Andrology Electron Transport Mitochondrial Proteins Fluorides Mice Oogenesis Follicular phase medicine Environmental Chemistry MFN1 Animals 0105 earth and related environmental sciences Granulosa Cells Chemistry Public Health Environmental and Occupational Health General Medicine General Chemistry Pollution 020801 environmental engineering Mitochondria medicine.anatomical_structure Mitochondrial respiratory chain mitochondrial fusion Apoptosis Female |
| Zdroj: | Chemosphere. 215 |
| ISSN: | 1879-1298 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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