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Calorie restriction does not influence oocyte quality in oocytes from POLG mitochondrial mutator mice
PLOS ONE ( IF 3.7 ) Pub Date : 2018-09-21 , DOI: 10.1371/journal.pone.0204373
Christine Faraci , Joyce Jin , Dori C. Woods

It has recently been demonstrated that moderate adult onset caloric restriction (e.g. calorie restriction; CR) has a positive impact on female fertility in aged mice, due in large to preventing the age-associated decline in the quality of oocytes available for fertilization. The impact of CR on oocyte quality has been attributed, at least in part, to mitochondrial functions. In mitochondrial DNA (mtDNA) mutator mice (PolgD257A/D257A), which harbor a mutation in the proofreading mtDNA polymerase-gamma (POLG), mitochondrial mutations rapidly accumulate, resulting in a premature aging phenotype and female infertility. As CR has been shown to extend both lifespan and ‘healthspan’ as well as improve oocyte quality in aged mice, we investigated whether adult onset CR could improve oocyte quality in the POLG mouse. Female PolgD257A/D257A mice exhibited infertility based on an inability to produce litters through natural mating. Analysis of oocytes from 8–9-month-old PolgD257A/D257A mice on CR following hormone stimulation revealed no improvement in the number of oocytes ovulated. Furthermore, CR did not result in a greater percentage of metaphase II oocytes, with the majority of the oocytes prematurely arrested at the germinal vesicle stage. Finally, CR did not improve the abnormal mitochondrial distribution or pronounced defects in meiotic spindle assembly and chromosomal distribution observed in the ad libitum fed PolgD257A/D257A. Taken together, these data suggest that although CR benefits oocyte quality and fertility outcomes in naturally aged female mice, it does not sufficiently improve oocyte quality in PolgD257A/D257A.



中文翻译:

热量限制不会影响POLG线粒体突变小鼠的卵母细胞的卵母细胞质量

最近已经表明,适度的成人发病热量限制(ē热量限制; CR)在老年小鼠对女性生育能力产生积极的影响,这在很大程度上防止与年龄相关的下降可用于受精的卵母细胞的质量。CR对卵母细胞质量的影响至少部分归因于线粒体功能。在线粒体DNA(mtDNA)突变小鼠中(Polg D257A / D257A)(在校正mtDNA聚合酶-γ(POLG)中带有突变),线粒体突变迅速积累,导致过早的表型和女性不育。由于CR已显示可延长衰老小鼠的寿命和“健康期”并改善其卵母细胞质量,因此我们研究了成年发作的CR是否可以改善POLG小鼠的卵母细胞质量。雌性Polg D257A / D257A小鼠由于无法通过自然交配而产下垫料,因此表现出不育性。分析8-9个月大的Polg D257A / D257A的卵母细胞荷尔蒙刺激后接受CR的小鼠显示,排卵的卵母细胞数量没有改善。此外,CR不会导致更大比例的II期中期卵母细胞,大多数卵母细胞过早地停滞在生小泡阶段。最后,CR不能改善在随意喂饲的Polg D257A / D257A中观察到的异常线粒体分布或减数分裂纺锤体组装和染色体分布中的明显缺陷。综上所述,这些数据表明,尽管CR有益于自然衰老的雌性小鼠的卵母细胞质量和育性结果,但它并不能充分改善Polg D257A / D257A中的卵母细胞质量。

更新日期:2018-09-22
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