Reproductive aging is associated with decreased mitochondrial abundance and altered structure in murine oocytes
Reproductive aging is associated with decreased mitochondrial abundance and altered structure in murine oocytes
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DOI：
10.1007/s10815-012-9771-5
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Lewis, William
中科院分区：
文献类型：
--
作者：
Kushnir, Vitaly A.;Ludaway, Tomika;Lewis, William
在我们的小鼠模型中建立生殖衰老表型。为了检验生殖老化与线粒体丰度降低相关的假设，这最终反映了卵母细胞的功能障碍，在年轻和年老的雌性未交配野生型C57 BL 6 J小鼠中进行育种研究，通过测量受孕时间、窝仔数和每只母鼠活产来建立它们的生殖表型。分析单个卵母细胞的mtDNA含量。用透射电镜观察卵母细胞线粒体的超微结构，发现高龄母鼠受孕时间明显延长，胎仔存活率降低。与年轻对照组相比，老年小鼠的卵母细胞的mtDNA少2.7倍（p < 0.001; 95%CI 2.1-3.5）。透射电子显微镜证实老年动物卵母细胞线粒体细胞器丰度减少。在线粒体中观察到明显的形态学变化，表明老年动物卵母细胞中线粒体生物发生的改变。衰老与卵母细胞中线粒体数量的显著减少有关。我们的数据支持线粒体细胞器的损失和功能障碍的卵母细胞作为一个潜在的病因生殖衰老。
To establish the phenotype of reproductive aging in our mouse model. To test the hypotheses that reproductive aging is associated with a decrease in mitochondrial abundance that could ultimately reflect dysfunction in oocytes.Breeding studies were performed in young and aged female virgin wild type C57BL6J mice to establish their reproductive phenotype by measuring time to conception, litter size, and live birth per dam. Individual oocytes were analyzed for mtDNA content. Transmission electron microscopy was used to study ultrastructure of mitochondria in oocytes.Old females were found to have significantly prolonged time to conception and fewer surviving pups in their litters. Oocytes from old mice had 2.7-fold less mtDNA compared to younger controls (p < 0.001; 95 % CI 2.1-3.5). Decrease in mitochondrial organelle abundance in old animal's oocytes was confirmed with transmission electron microscopy. Distinct morphological changes were noted in mitochondria, suggesting altered mitochondrial biogenesis in the old animals' oocytes.Reproductive aging in mice is associated with reduced reproductive competence. Aging is associated with a significant decrease in number of mitochondria in oocytes. Our data support mitochondrial organelle loss and dysfunction in oocytes as a potential etiology for reproductive senescence.