Blood cell mitochondrial DNA content and premature ovarian aging.

Blood cell mitochondrial DNA content and premature ovarian aging.
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DOI:
10.1371/journal.pone.0042423
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Italian Network for the study of Ovarian Dysfunctions
Italian Network for the study of Ovarian Dysfunctions
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bonomi M;Somigliana E;Cacciatore C;Busnelli M;Rossetti R;Bonetti S;Paffoni A;Mari D;Ragni G;Persani L;Italian Network for the study of Ovarian Dysfunctions

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原发性卵巢功能不全(POI)是一种严重的生育缺陷,其特征是卵泡储备的预期和沉默的损害,但其发病机制在很大程度上是无法解释的。POI的频繁母系遗传,以及卵巢卵泡发生对线粒体生物发生和生物能量学的显著依赖,表明可能涉及广义线粒体缺陷。在这里,我们验证了一组接受卵巢过度刺激(OH)的妇女血液和卵巢线粒体DNA(mtDNA)含量之间存在显着相关性,然后旨在验证POI妇女血细胞中mtDNA含量是否显着改变。我们招募了101名卵巢储备功能受损的妇女:59名卵巢早衰(POF)妇女和42名对OH反应不良(PR)的妇女。Taqman拷贝数分析显示POF和PR妇女与43名年龄相似且卵巢储备完整的妇女或53名有生理性绝经史的高龄妇女相比,mtDNA明显缺失(P<0.001)。在57例血mtDNA含量低的POF或PR妇女中未检测到线粒体DNA聚合酶γ(POLG)基因的致病变异。总之,血细胞线粒体DNA耗竭是卵巢早衰妇女中的常见现象,这表明一个尚未确定但普遍存在的线粒体缺陷可能经常易患POI,而POI则可以被认为是一种预期的衰老形式,其中卵巢缺陷可能是第一个表现。血液中mtDNA含量的测定可能成为POI风险预测的有用工具。
Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.
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