The Ratio of cf-mtDNA vs. cf-nDNA in the Follicular Fluid of Women Undergoing IVF Is Positively Correlated with Age

Georgia Tsirka; Athanasios Zikopoulos; Kyriaki Papageorgiou; Charilaos Kostoulas; Ioannis Tsigkas; Efthalia Moustakli; Aris Kaltsas; Eleftheria Sarafi; Theologos M Michaelidis; Ioannis Georgiou

doi:10.3390/genes14071504

The Ratio of cf-mtDNA vs. cf-nDNA in the Follicular Fluid of Women Undergoing IVF Is Positively Correlated with Age

Genes (Basel). 2023 Jul 23;14(7):1504. doi: 10.3390/genes14071504.

Authors

Affiliations

¹ Laboratory of Medical Genetics in Clinical Practice, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
² Obstetrics and Gynecology, Royal Cornwall Hospital, Truro TR1 3LQ, UK.
³ Department of Biological Applications & Technology, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
⁴ Biomedical Research Institute, Foundation for Research and Technology-Hellas, 45115 Ioannina, Greece.
⁵ Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.

Abstract

Age-related mitochondrial markers may facilitate the prognosis of artificial reproductive technology outcomes. In this report, we present our study concerning the ratio of cf-mtDNA/cf-nDNA, namely the amount of cell-free mitochondrial DNA relative to cell-free nuclear DNA, in the follicular fluid (FF) of women undergoing IVF, aiming to generate a molecular fingerprint of oocyte quality. The values of this ratio were measured and compared among three groups of women (101 in total): (A) 31 women with polycystic ovary syndrome (PCOS), (B) 34 women younger than 36 years, and (C) 36 women older than 35 years of age. Real-time quantitative PCR (qPCR) was performed to quantify the ratio by using nuclear- and mitochondrial-specific primers and analyzed for potential correlation with age and pregnancy rate. Our analysis showed that the level of FF-cf-mtDNA was lower in the group of advanced-age women than in the groups of PCOS and non-PCOS women. Moreover, a significant positive correlation between FF-cf-mtDNA and the number of mature (MII) oocytes was observed. Collectively, the data show that the relative ratio of cf- mtDNA to cf-nDNA content in human FF can be an effective predictor for assessing the corresponding oocyte's age-related performance in IVF.

Keywords: ART; IVF; PCOS; age; cf-mtDNA; cf-mtDNA/cf-nDNA; cf-nDNA; follicular fluid (FF); mitochondria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA, Mitochondrial / genetics
DNA, Mitochondrial / metabolism
Female
Fertilization in Vitro
Follicular Fluid* / metabolism
Humans
Mitochondria
Oocytes / metabolism
Polycystic Ovary Syndrome* / genetics
Pregnancy

Substances

DNA, Mitochondrial

Grants and funding

This work was funded by the project “Understanding pathways of healthy ageing (in health and disease) through the integration of high-resolution omics data—pathAGE” (MIS 5047228) which is implemented under the Action “Regional Excellence in R&D Infrastructures”, funded by the Operational Programme “Competitiveness, Entrepreneurship, and Innovation” (NSRF 2014–2020) and cofinanced by Greece and the European Union (European Regional Development Fund).