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Elevated cell-free mitochondria DNA level of patients with premature ovarian insufficiency
Xing-Yu Zhou1, Yi-Zhen Yang1, Jun Zhang1
1Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Northern Road, Guangzhou, 510515, Guangdong, China.
Background:
Premature ovarian insufficiency (POI) patients present with a chronic inflammatory state. Cell-free mitochondria DNA (cf-mtDNA) has been explored as a reliable biomarker for estimating the inflammation-related disorders, however, the cf-mtDNA levels in POI patients have never been measured. Therefore, in the presenting study, we aimed to evaluate the levels of cf-mtDNA in plasma and follicular fluid (FF) of POI patients and to determine a potential role of cf-mtDNA in predicting the disease progress and pregnancy outcomes.
Methods:
We collected plasma and FF samples from POI patients, biochemical POI (bPOI) patients and control women. Quantitative real-time PCR was used to measure the ratio of mitochondrial genome to nuclear genome of cf-DNAs extracted from the plasma and FF samples.
Results:
The plasma cf-mtDNA levels, including COX3, CYB, ND1 and mtDNA79, were significantly higher in overt POI patients than those in bPOI patients or control women. The plasma cf-mtDNA levels were weakly correlated with ovarian reserve, and could not be improved by regular hormone replacement therapy. The levels of cf-mtDNA in FF, rather than those in plasma, exhibited the potential to predict the pregnancy outcomes, although they were comparable among overt POI, bPOI and control groups.
Conclusions:
The increased plasma cf-mtDNA levels in overt POI patients indicated its role in the progress of POI and the FF cf-mtDNA content may hold the value in predicting pregnancy outcomes of POI patients.
Insights
Elevated cell-free mitochondrial DNA (cf-mtDNA) in plasma indicates premature ovarian insufficiency (POI) progression. Follicular fluid cf-mtDNA may predict pregnancy outcomes in POI patients.
Area of Science:
- Reproductive Endocrinology
- Mitochondrial Biology
- Biomarker Discovery
Background:
- Premature ovarian insufficiency (POI) is associated with a chronic inflammatory state.
- Cell-free mitochondrial DNA (cf-mtDNA) is a potential biomarker for inflammation-related disorders.
- cf-mtDNA levels in POI patients have not been previously investigated.
Purpose of the Study:
- To evaluate cf-mtDNA levels in plasma and follicular fluid (FF) of POI patients.
- To determine the potential role of cf-mtDNA in predicting POI disease progression.
- To assess cf-mtDNA's utility in predicting pregnancy outcomes for POI patients.
Main Methods:
- Collected plasma and FF samples from POI patients, biochemical POI (bPOI) patients, and control women.
- Utilized quantitative real-time PCR to measure the ratio of mitochondrial to nuclear genomes in cf-DNAs.
- Analyzed cf-mtDNA levels in both plasma and FF samples.
Main Results:
- Plasma cf-mtDNA levels (COX3, CYB, ND1, mtDNA79) were significantly higher in overt POI patients compared to bPOI patients and controls.
- Plasma cf-mtDNA showed a weak correlation with ovarian reserve and was not improved by hormone replacement therapy.
- Follicular fluid cf-mtDNA, not plasma cf-mtDNA, showed potential for predicting pregnancy outcomes, despite comparable levels across groups.
Conclusions:
- Increased plasma cf-mtDNA levels in overt POI patients suggest a role in disease progression.
- Follicular fluid cf-mtDNA content may be valuable for predicting pregnancy outcomes in POI patients.
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