Background

The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN’s effect.

Methods

Streptozotocin (STZ) was used to establish the mouse models with type 1 diabetes. The successful establishment of the models was confirmed by the results of body weight test, fasting blood glucose test and haematoxylin and eosin (H&E) staining. The in vitro maturation (IVM) rate of oocytes from diabetic mice was examined. Immunofluorescence staining (IF) was performed to examine the reactive oxygen species (ROS) level, spindle/chromosome structure, mitochondrial function, actin dynamics, DNA damage and histone modification of oocytes, which are potential factors affecting the oocyte quality. The quantitative reverse transcription PCR (RT-qPCR) was used to detect the mRNA levels of Sod1, Opa1, Mfn2, Drp1, Sirt1 and Sirt3 in oocytes.

Results

The NMN supplementation increased the oocyte maturation rate of the mice with diabetes. Furthermore, NMN supplementation improved the oocyte quality by rescuing the actin dynamics, reversing meiotic defects, improving the mitochondrial function, reducing ROS level, suppressing DNA damage and restoring changes in histone modifications of oocytes collected from the mice with diabetes.

Conclusion

NMN could improve the maturation rate and quality of oocytes in STZ-induced diabetic mice, which provides a significant clue for the treatment of infertility of the patients with diabetes.

中文翻译：

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烟酰胺单核苷酸可改善 1 型糖尿病小鼠的卵母细胞成熟

背景

近年来，全球1型糖尿病患者数量迅速增加。由于卵母细胞质量下降，母亲糖尿病对生殖结果产生不利影响。然而，提高患有糖尿病的不孕女性的卵母细胞质量和人工生殖技术（ART）效率的策略尚未得到充分研究。在本研究中，我们旨在检测烟酰胺单核苷酸（NMN）对1型糖尿病小鼠卵母细胞成熟的影响，并探讨NMN作用的潜在机制。

方法

使用链脲佐菌素（STZ）建立1型糖尿病小鼠模型。体重测定、空腹血糖测定、苏木精和伊红(H&E)染色结果证实模型建立成功。检查了糖尿病小鼠卵母细胞的体外成熟（IVM）率。免疫荧光染色（IF）检查卵母细胞的活性氧（ROS）水平、纺锤体/染色体结构、线粒体功能、肌动蛋白动态、DNA损伤和组蛋白修饰，这些是影响卵母细胞质量的潜在因素。采用定量逆转录PCR（RT-qPCR）检测卵母细胞中Sod1、Opa1、Mfn2、Drp1、Sirt1、Sirt3 mRNA水平。

结果

补充 NMN 提高了糖尿病小鼠的卵母细胞成熟率。此外，补充 NMN 可以通过挽救糖尿病小鼠卵母细胞的肌动蛋白动力学、逆转减数分裂缺陷、改善线粒体功能、降低 ROS 水平、抑制 DNA 损伤和恢复组蛋白修饰的变化来改善卵母细胞质量。

结论

NMN可提高STZ诱导的糖尿病小鼠卵母细胞的成熟率和质量，为糖尿病患者不孕症的治疗提供重要线索。