二甲双胍可增强高血糖和高血脂条件下培养的卵母细胞中除纺锤体组织外的主要细胞质组织:体外研究

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
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引用次数: 0

摘要

本研究旨在探讨抗糖尿病药物二甲双胍对卵母细胞胞质组织的作用。从成年雌性瑞士白化小鼠体内采集胚泡期(GV)卵母细胞,在不同的实验组--对照组、载体对照组(0.3%乙醇)、二甲双胍组(50 μg/mL)、高糖高脂组(HGHL,在乙醇中加入10 mM葡萄糖、150 μM棕榈酸、75 μM硬脂酸和200 μM油酸)和添加二甲双胍的HGHL组--进行体外成熟(IVM)。研究人员分析了分裂期 II(MII)卵母细胞的脂质积累、线粒体和内质网(ER)分布模式、氧化和 ER 应激、肌动蛋白丝组织、皮质颗粒分布模式、纺锤体组织和染色体排列。HGHL 组观察到极体早期挤出。然而,与对照组相比,各实验组在 24 小时内的成熟率并无显著差异。与对照组相比,HGHL 条件下的氧化应激、ER 应激、肌动蛋白丝组织不良、脂质积累增加、线粒体分布改变、纺锤体异常和染色体错位水平明显更高。除纺锤体组织外,在HGHL条件下补充二甲双胍可改善所有参数(ER和肌动蛋白分布模式不显著)。这些结果表明,在培养基中添加二甲双胍有助于改善高血糖和高脂血症诱导的细胞质异常,但纺锤体组织除外。鉴于纺锤体组织在卵母细胞成熟和减数分裂恢复过程中染色体正常分离的关键作用,二甲双胍在这方面的局限性值得仔细评估和进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metformin augments major cytoplasmic organization except for spindle organization in oocytes cultured under hyperglycemic and hyperlipidemic conditions: An in vitro study

The present study aimed to investigate the role of antidiabetic drug metformin on the cytoplasmic organization of oocytes. Germinal vesicle (GV) stage oocytes were collected from adult female Swiss albino mice and subjected to in vitro maturation (IVM) in various experimental groups- control, vehicle control (0.3% ethanol), metformin (50 μg/mL), high glucose and high lipid (HGHL, 10 mM glucose; 150 μM palmitic acid; 75 μM stearic acid and 200 μM oleic acid in ethanol), and HGHL supplemented with metformin. The metaphase II (MII) oocytes were analyzed for lipid accumulation, mitochondrial and endoplasmic reticulum (ER) distribution pattern, oxidative and ER stress, actin filament organization, cortical granule distribution pattern, spindle organization and chromosome alignment. An early polar body extrusion was observed in the HGHL group. However, the maturation rate at 24 h did not differ significantly among the experimental groups compared to the control. The HGHL conditions exhibited significantly higher levels of oxidative stress, ER stress, poor actin filament organization, increased lipid accumulation, altered mitochondrial distribution, spindle abnormalities, and chromosome misalignment compared to the control. Except for spindle organization, supplementation of metformin to the HGHL conditions improved all the parameters (non-significant for ER and actin distribution pattern). These results show that metformin exposure in the culture media helped to improve the hyperglycemia and hyperlipidemia-induced cytoplasmic anomalies except for spindle organization. Given the crucial role of spindle organization in proper chromosome segregation during oocyte maturation and meiotic resumption, the implications of metformin's limitations in this aspect warrant careful evaluation and further investigation.

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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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