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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

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posted on 2023-07-19, 10:53 authored by Maryam Qasemi, Ashraf Aleyasin, Reza Mahdian, Nasrin Ghanami GashtiNasrin Ghanami Gashti, Maryam Shabani Nashtaei, Zhaleh Ashrafnezhad, Fardin Amidi

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.

History

Publication

Mitochondrion, 2021 59, pp. 30-36

Publisher

Elsevier

Other Funding information

The study was supported by Tehran University of Medical Sciences (Grant number: 97-02-30-38748)

Rights

This is the author’s version of a work that was accepted for publication in Mitochondrion. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mitochondrion,Volume 59,2021,Pages 30-36, https://doi.org/10.1016/j.mito.2021.04.003

Department or School

  • School of Engineering

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