Atg9A-mediated mitophagy is required for decidual differentiation of endometrial stromal cells |
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| Institution: | 1. Department of Gynecology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China;2. Department of Orthopedics, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China;1. Department of Obstetrics, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan Hubei Province 430015, China;2. Department of Pathology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan Hubei Province 430015, China;1. Health Management Center, Huizhou Central People''s Hospital, Huizhou, Guangdong, China;2. Department of Stomatology, Huizhou Central People''s Hospital, Huizhou, Guangdong, China;3. Department of Breast Surgery, Huizhou Central People''s Hospital, Huizhou, Guangdong, China;1. State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Animal Reproduction Institute, College of Animal Science and Technology, Guangxi University, Nanning 530004, China;2. Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China;3. Key Laboratory of Animal Breeding and Reproduction, Institute of Animal Science, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China;4. Suqian Institute of Agricultural Sciences, Jiangsu Academy of Agricultural Sciences, Suqian 223800, China;5. Reproductive Medical Center, Renmin Hospital of Wuhan University, JieFang Road 238, Wuhan 430060, China;1. Department of Oncology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China;2. Department of Gynecology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong, China |
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| Abstract: | Endometrial decidualization is the foundation of a healthy pregnancy. Mitochondrial dysfunction is an independent cause of disease for energy-intensive organs. Mitochondrial homeostasis plays a key role in the differentiation processes of many cell types. We showed increased activation of mitophagy (mitochondrial autophagy) in the decidua compared with proliferative or secretory endometrium. To better comprehend the mechanisms underlying healthy conception, understanding the mechanism of endometrial stromal cell decidualization is of great importance. Here, we artificially induced decidualization of a human endometrial stromal cell line (T HESCs) and characterized subsequent activation of mitophagy using immunofluorescence assay, electron microscopy and Western blot assay. Knockdown of autophagy-related 9A (ATG9A) led to an obvious reduction of mitophagy and deficiencies in decidualization. Our findings demonstrate a key role for proper mitochondrial dynamics in decidual differentiation and identify ATG9A-mediated mitophagy as a novel therapeutic target for repeated implantation failure or recurrent abortion. |
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| Keywords: | Mitophagy Decidualization ATG9A Differentiation Human endometrial stromal cell line |
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