SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation |
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| Authors: | Juan Zeng Manxi Jiang Xinghan Wu Feiyang Diao Danhong Qiu Xiaojing Hou Haichao Wang Ling Li Chunling Li Juan Ge Jiayin Liu Xianghong Ou Qiang Wang |
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| Affiliation: | 1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China;2. Fertility Preservation Laboratory, Human Reproduction Medical Center, Guangdong Second Provincial General Hospital, Guangzhou, China;3. Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China |
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| Abstract: | SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293‐PDHE1α mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age‐associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality. |
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| Keywords: | aging meiosis metabolism oocyte SIRT4 |
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