Desquiret-Dumas V, Clément A, Seegers V, Boucret L, Ferré-L'Hotellier V, Bouet P E, Descamps P, Procaccio V, Reynier P, May-Panloup P
Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.
PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France.
Hum Reprod. 2017 Mar 1;32(3):607-614. doi: 10.1093/humrep/dew341.
Could the mitochondrial DNA (mtDNA) content of cumulus granulosa cells (CGCs) be related to oocyte competence?
The quality of embryos obtained during IVF procedures appears to be linked to mtDNA copy numbers in the CGCs.
Oocyte quality is linked to oocyte mtDNA content in the human and other species, and the mtDNA copy number of the oocyte is related to that of the corresponding CGCs. Moreover, the quantification of CGC mtDNA has recently been proposed as a biomarker of embryo viability.
STUDY DESIGN SIZE, DURATION: An observational study was performed on 452 oocyte-cumulus complexes retrieved from 62 patients undergoing ICSI at the ART Center of the University Hospital of Angers, France, from January to May 2015.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. The relationship between CGC mtDNA content and oocyte maturity and fertilizability, on one hand, and embryo quality, on the other, was investigated using univariate and multivariate generalized models with fixed and mixed effects.
No relationship was found between CGC mtDNA content and oocyte maturity or fertilizability. In contrast, there was a significant link between the content of mtDNA in CGCs surrounding an oocyte and the embryo quality, with significantly higher mtDNA copy numbers being associated with good quality embryos compared with fair or poor quality embryos [interquartile range, respectively, 738 (250-1228) and 342 (159-818); P = 0.006]. However, the indication provided by the quantification of CGC mtDNA concerning the eventuality of good embryo quality was seriously subject to patient effect (AUC = 0.806, 95%CI = 0.719-0.869). The quantity of CGC mtDNA was influenced by BMI and smoking.
N/A.
The quantification of CGC mtDNA may indicate embryo quality. However, since it is affected by patient specificity, it should be used with caution. It remains to be seen whether this marker could directly predict the implantation capacity of the embryo, which is the main objective in IVF practice.
Our study suggests that the quantification of CGC mtDNA may be a novel biomarker of embryo viability. However, patient specificity makes it impossible to establish a general threshold value, valid for all patients. Nevertheless, further studies are needed to determine whether the quantification of CGC mtDNA may, in combination with the morpho-kinetic method, offer an additional criterion for selecting the best embryo for transfer from a given cohort.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centres INSERM and the CNRS. There were no competing interests.
卵丘颗粒细胞(CGCs)的线粒体DNA(mtDNA)含量是否与卵母细胞质量有关?
体外受精过程中获得的胚胎质量似乎与CGCs中的mtDNA拷贝数有关。
在人类和其他物种中,卵母细胞质量与卵母细胞mtDNA含量有关,且卵母细胞的mtDNA拷贝数与相应的CGCs的mtDNA拷贝数相关。此外,最近有人提出对CGC mtDNA进行定量可作为胚胎活力的生物标志物。
研究设计规模、持续时间:2015年1月至5月,在法国昂热大学医院ART中心对62例行卵胞浆内单精子注射(ICSI)的患者获取的452个卵母细胞-卵丘复合体进行了一项观察性研究。
参与者/材料、环境、方法:采用定量实时PCR技术评估CGCs的平均mtDNA含量。一方面,使用具有固定效应和混合效应的单变量和多变量广义模型研究CGC mtDNA含量与卵母细胞成熟度和受精能力之间的关系;另一方面,研究其与胚胎质量之间的关系。
未发现CGC mtDNA含量与卵母细胞成熟度或受精能力之间存在关联。相反,卵母细胞周围CGCs中的mtDNA含量与胚胎质量之间存在显著联系,与质量一般或较差的胚胎相比,质量良好的胚胎的mtDNA拷贝数明显更高[四分位间距分别为738(250 - 1228)和342(159 - 818);P = 0.006]。然而,CGC mtDNA定量所提供的关于优质胚胎可能性的指标受患者效应影响严重(曲线下面积 = 0.806,95%置信区间 = 0.719 - 0.869)。CGC mtDNA的量受体重指数(BMI)和吸烟影响。
无。
局限性、谨慎原因:CGC mtDNA定量可能表明胚胎质量。然而,由于它受患者特异性影响,应谨慎使用。该标志物能否直接预测胚胎的着床能力,这在体外受精实践中是主要目标,仍有待观察。
我们的研究表明,CGC mtDNA定量可能是一种新的胚胎活力生物标志物。然而,患者特异性使得无法建立适用于所有患者的通用阈值。尽管如此,仍需要进一步研究以确定CGC mtDNA定量是否可以与形态动力学方法相结合,为从给定队列中选择最佳移植胚胎提供额外标准。
研究资金/竞争利益:这项工作得到了昂热大学医院、法国昂热大学以及法国国家研究中心法国国家健康与医学研究院(INSERM)和法国国家科学研究中心(CNRS)的支持。不存在竞争利益。