Perfluorooctanoic acid (PFOA) inhibits the gap junction intercellular communication and induces apoptosis in human ovarian granulosa cells |
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| Institution: | 1. Department of Reproductive Endocrinology, Women''s Hospital, School of Medicine, Zhejiang University, Hangzhou, China;2. Reproductive Medical Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;3. Department of Gynecology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China;1. Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China;2. University of Chinese Academy of Science, Beijing 100049, China;3. Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Municipal Center for Disease Control and Prevention, Zhejiang Zhoushan, 316021, China;4. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK;1. Department of Clinical Sciences, Swedish University of Agricultural Science (SLU), Box 7054, SE-750 07, Uppsala, Sweden;2. Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7036, SE-750 07, Uppsala, Sweden;3. Centre for Reproductive Biology in Uppsala, P.O Box 7054, SE-750 07, Uppsala, Sweden;4. Swedish Museum of Natural History, P.O Box 50007, SE-104 05, Stockholm, Sweden;1. Department of Pediatrics, Peking University First Hospital, No.1 Xi''an Men Street, West District, Beijing, 100034, China;2. Department of Pediatrics, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China;3. Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, 510632, China;4. Department of Anesthesiology, Center of Scientific Research, The Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China;1. College of Life and Environmental Sciences, Hangzhou Normal University, Xuelin Road 16#, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province, 310036, China;2. Guangzhou Key Laboratory of Environmental Exposure and Health, School of Environment, Jinan University, Guangzhou, 510632, China;3. Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou, 310036, China;1. School of Forestry and Bio-technology, Zhejiang Agricultural & Forestry University, Hangzhou, Zhejiang, 311300, China;2. School of Science, Zhejiang Agricultural & Forestry University, Hangzhou, Zhejiang, 311300, China;1. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China;2. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China;3. Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China;4. Jiangsu Provincial Center for Diseases Control and Prevention, Nanjing 210009, China |
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| Abstract: | Perfluorooctanoic acid (PFOA) has attracted widespread research attention as it is very stable, bioaccumulates, and causes reproductive toxicity. Data from several animal experiments and epidemiological studies indicate that female fertility may decline because of ovarian granulosa cell (GC) apoptosis as oocyte quality is positively associated with effective gap junctional intercellular communication (GJIC) between GCs. To the best of our knowledge, however, no previous trials have been conducted or reported on the effects of PFOA exposure on apoptosis induction in human GCs. Moreover, the roles of GJIC in GC survival and in the induction of apoptosis in GCs by PFOA remain unclear. To test this, we cultured human GCs in vitro and treated them with 0 μM, 0.3 μM, 3 μM, or 30 μM PFOA for 24 h. We also treated a human ovarian GC line (KGN) with various combinations of PFOA, retinoic acid (RA, 10 μM), and carbenoxolone disodium (CBX, 50 mM). Our findings showed that PFOA lowered human GC viability and increased apoptosis. The effects of CBX resemble those of PFOA. The combination of PFOA and CBX enhances the inhibition of GJIC by PFOA and promotes apoptosis. The effects of RA are the opposite to those of PFOA. The combination of RA and PFOA mitigates PFOA-induced GJIC inhibition and reduces apoptosis. The observed expression levels of apoptosis-related proteins were consistent with the aforementioned findings. Hence, our study demonstrated that PFOA may induce human ovarian GC apoptosis by inhibiting GJIC. |
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| Keywords: | Apoptosis Gap junction Intercellular communication Ovarian granulosa cell Perfluorooctanoic acid |
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