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Cell-free mtDNA level and its biomarker potency for ART outcome are different in follicular fluid of PCOS and non-PCOS women
Mitochondrion ( IF 3.9 ) Pub Date : 2021-04-09 , DOI: 10.1016/j.mito.2021.04.003
Maryam Qasemi 1 , Ashraf Aleyasin 2 , Reza Mahdian 3 , Nasrin Ghanami Gashti 1 , Maryam Shabani Nashtaei 4 , Zhaleh Ashrafnezhad 1 , Fardin Amidi 4
Affiliation  

Introduction

Lack of reliable biomarkers for estimating the outcome is one of the current gaps in ART. In this study, we assessed whether cell-free mitochondrial DNA within the follicular fluid (FF cf-mtDNA) of PCOS patients has biomarker applicability or not. Furthermore, probable involved mechanisms in the FF cf-mtDNA pathway were evaluated.

Methods

The level of FF cf-mtDNA was compared between 50 PCOS patients and 50 women without any certain reproductive disorder, and analyzed for correlations with ART outcome. The associations between levels of FF cf-mtDNA and TFAM, POLG, and RNase H1 genes expression in mural granulosa cells (MGCs), as well as IL-6, and TNFα in follicular fluid (FF) were assessed.

Results

We identified that FF cf-mtDNA level was significantly lower in PCOS women and was accompanied by a reduction in the expression of mtDNA biogenesis genes in MGCs of the patients. Although a significant association between FF cf-mtDNA level and ART outcome was observed in the control group, no correlation could be proved in the PCOS group. Moreover, the expression level of TFAM was negatively associated, while amounts of IL-6 and TNFα were positively correlated with FF cf-mtDNA level in both groups.

Conclusion

PCOS patients present a lower FF cf-mtDNA level in comparison with non-PCOS women. FF cf-mtDNA has biomarker applicability for ART outcome in women without any certain reproductive disorder, but not for those with PCOS. It seems that mtDNA packaging dysfunction results in elevated FF cf-mtDNA, and subsequent effects are triggered by increasing the inflammatory cytokines.



中文翻译:

PCOS 和非 PCOS 女性的卵泡液中的游离 mtDNA 水平及其对 ART 结果的生物标志物效力不同

介绍

缺乏用于估计结果的可靠生物标志物是目前 ART 的空白之一。在本研究中,我们评估了 PCOS 患者卵泡液 (FF cf-mtDNA) 中的无细胞线粒体 DNA 是否具有生物标志物的适用性。此外,还评估了 FF cf-mtDNA 通路中可能涉及的机制。

方法

比较了 50 名 PCOS 患者和 50 名没有任何特定生殖障碍的女性的 FF cf-mtDNA 水平,并分析了与 ART 结果的相关性。评估了壁颗粒细胞 (MGC)中 FF cf-mtDNA 水平与TFAMPOLGRNase H1基因表达以及卵泡液 (FF) 中 IL-6 和 TNFα 水平之间的关联。

结果

我们发现 PCOS 女性的 FF cf-mtDNA 水平显着降低,并且伴随着患者 MGC 中 mtDNA 生物发生基因表达的降低。虽然在对照组中观察到 FF cf-mtDNA 水平与 ART 结果之间存在显着关联,但在 PCOS 组中无法证明相关性。此外,TFAM 的表达水平呈负相关,而 IL-6 和 TNFα 的量与 FF cf-mtDNA 水平呈正相关。

结论

与非 PCOS 女性相比,PCOS 患者的 FF cf-mtDNA 水平较低。FF cf-mtDNA 对没有任何特定生殖障碍的女性的 ART 结局具有生物标志物适用性,但不适用于患有 PCOS 的女性。似乎 mtDNA 包装功能障碍导致 FF cf-mtDNA 升高,随后的影响是通过增加炎性细胞因子来触发的。

更新日期:2021-04-20
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