Involvement of SIRT3‐GSK3β deacetylation pathway in the effects of maternal diabetes on oocyte meiosis
| العنوان: | Involvement of SIRT3‐GSK3β deacetylation pathway in the effects of maternal diabetes on oocyte meiosis |
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| المؤلفون: | Juan Ge, Qiang Wang, Longsen Han, Congyang Li, Yifei Jin, Shuai Zhu, Danni Wang, Yongan Xin, Zhenyue Huang |
| المصدر: | Cell Proliferation |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Mutant, Biology, medicine.disease_cause, Streptozocin, Diabetes Mellitus, Experimental, Mice, 03 medical and health sciences, 0302 clinical medicine, Meiosis, Sirtuin 3, medicine, Animals, oxidative stress, Sirtuin, oocyte, Cells, Cultured, Mice, Inbred ICR, Gene knockdown, Mutation, Glycogen Synthase Kinase 3 beta, diabetes, Acetylation, Original Articles, Cell Biology, General Medicine, Oocyte, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Oocytes, biology.protein, Female, Original Article, Injections, Intraperitoneal, Immunostaining |
| الوصف: | Objectives It has been widely reported that maternal diabetes impairs oocyte quality. However, the responsible mechanisms remain to be explored. In the present study, we focused on whether SIRT3‐GSK3β pathway mediates the meiotic defects in oocytes from diabetic mice. Materials and methods GSK3β functions in mouse oocyte meiosis were first detected by targeted siRNA knockdown. Spindle assembly and chromosome alignment were visualized by immunostaining and analysed under the confocal microscope. PCR‐based site mutation of specific GSK3β lysine residues was used to confirm which lysine residues function in oocyte meiosis. siRNA knockdown coupled with cRNA overexpression was performed to detect SIRT3‐GSK3β pathway functions in oocyte meiosis. Immunofluorescence was performed to detect ROS levels. T1DM mouse models were induced by a single intraperitoneal injection of streptozotocin. Results In the present study, we found that specific depletion of GSK3β disrupts maturational progression and meiotic apparatus in mouse oocytes. By constructing site‐specific mutants, we further revealed that acetylation state of lysine (K) 15 on GSK3β is essential for spindle assembly and chromosome alignment during oocyte meiosis. Moreover, non–acetylation‐mimetic mutant GSK3β‐K15R is capable of partly preventing the spindle/chromosome anomalies in oocytes with SIRT3 knockdown. A significant reduction in SIRT3 protein was detected in oocytes from diabetic mice. Of note, forced expression of GSK3β‐K15R ameliorates maternal diabetes‐associated meiotic defects in mouse oocytes, with no evident effects on oxidative stress. Conclusion Our data identify GSK3β as a cytoskeletal regulator that is required for the assembly of meiotic apparatus, and discover a beneficial effect of SIRT3‐dependent GSK3β deacetylation on oocyte quality from diabetic mice. Diabetic oocytes display a reduction in SIRT3 protein and show higher frequency of spindle/chromosome defects and excessive ROS. Deacetylation‐mimetic mutant GSK3β‐K15R alleviates the meiotic defects in oocytes from diabetic mice, while it was unable to decrease the ROS level in diabetic oocytes. |
| تدمد: | 1365-2184 0960-7722 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dcbcb580a9793b8f5c55089d41591ee5 https://doi.org/10.1111/cpr.12940 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dcbcb580a9793b8f5c55089d41591ee5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652184 09607722 |
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