Microgravity-induced disruption of mitochondria-spindle-chromosome coordination causes meiosis defects in mouse oocyte
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摘要: 本研究采用地基模拟微重力效应装置,研究微重力对小鼠卵母细胞减数分裂及成熟质量的影响,旨在为进一步研究空间环境对卵母细胞成熟的损伤机制提供重要的生物学参考. 利用芯片装载未成熟卵母细胞 (GV),通过随机定位仪进行小鼠卵母细胞成熟培养,分别对GV期、GVBD期、Pro-MⅠ期、MⅠ期、MⅡ期线粒体、纺锤体和染色体进行荧光成像. 微重力效应导致卵母细胞成熟率显著下降32.75% (p<0.01). 荧光成像显示,与正常重力相比,微重力加剧MⅠ期卵母细胞核周线粒体环状聚集构象;MⅡ期,细胞质中线粒体无规律聚集占比显著增多 (71.88%). 此外,微重力引发MⅠ期纺锤体多极化,导致染色体排布紊乱,最终导致MⅡ期纺锤体组装和染色体中板宽度异常,分别为57.58% (p<0.05)和15.63 μm (p<0.0001). 本研究表明,微重力效应通过干扰小鼠卵母细胞线粒体-纺锤体-染色体的动态协调,导致减数分裂异常和质量下降,对揭示力学干扰如何通过调控亚细胞结构互作网络影响卵母细胞质量具有重要意义.Abstract: This study employed a ground-based microgravity analog system to assess mouse oocyte meiotic progression and developmental competence, providing mechanistic insights into space environment-induced defects during oocyte maturation. Germinal vesicle (GV)-stage mouse oocytes were encapsulated in polydimethylsiloxane (PDMS) chip chamber and subjected to simulated microgravity (SMG) culture using a random positioning machine (RPM). Meiotic dynamics were systematically analyzed at five key stages: GV (0 h), GV breakdown (GVBD, 2 h), pro-metaphase I (Pro-MⅠ, 5 h), metaphase I (MⅠ, 8 h), and metaphase II (MⅡ, 16 h). Mitochondrial distribution, spindle morphology, and chromosome alignment were quantified through confocal laser microscopy coupled with fluorescent probes. The results showed that SMG exposure reduced oocyte maturation rates by 32.75% compared to normal gravity (NG) controls (p<0.01). Mitochondrial dynamics exhibited stage-specific perturbations: perinuclear clustering at MI (70.00% vs 41.18% in NG) and disorganized aggregation patterns in 71.88% of MII oocytes. Spindle assembly and chromosome alignment were also disrupted: multipolar spindles during MⅠ caused disordered chromosome segregation. At MⅡ, SMG oocytes displayed exacerbated spindle defects (57.58% abnormality rate vs 22.32% in NG, p<0.05) and widened equatorial plates (15.63 μm vs 7.55 μm, p<0.0001). These findings suggest that SMG exposure compromises meiosis and oocyte quality through tripartite disruption of mitochondrial-spindle-chromosomal coordination. These results provide important insights into how mechanical perturbations regulate subcellular structure interaction networks to affect oocyte quality.
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Key words:
- Oocyte /
- Microgravity /
- Mitochondria /
- Spindle /
- Chromosome
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