Deep sequencing shows that accumulation of potentially pathogenic mtDNA mutations rather than mtDNA copy numbers may...

Area of Science:

• Genetics
• Reproductive Biology
• Mitochondrial Biology

Background:

• Mitochondrial DNA (mtDNA) plays a crucial role in cellular energy production.
• Alterations in mtDNA quantity and mutations are implicated in various diseases and pregnancy complications.
• Understanding the link between mtDNA and early embryonic loss is vital for reproductive health.

Purpose of the Study:

• To investigate the association between mitochondrial DNA quantity and heteroplasmy with early embryonic loss.
• To determine if mtDNA copy number or pathogenic mutations correlate with spontaneous abortion (SA) or aneuploidy.

Main Methods:

• Collected 150 villous samples from spontaneous abortion (n=75) and induced abortion (n=75) groups.
• Utilized quantitative PCR (qPCR) and next-generation sequencing (NGS) to assess mtDNA quantity and heteroplasmy.
• Defined potentially pathogenic mutations as missense mutations with a CADD score > 15 and heteroplasmy ≥ 70%.

Main Results:

• No significant difference in mtDNA copy numbers was observed between SA and IA groups, nor between euploid and aneuploid groups.
• mtDNA copy numbers were not associated with spontaneous abortion via logistic regression analysis.
• A higher prevalence of possibly pathogenic mtDNA mutations was found in the SA group (70.7%) compared to the IA group (54.7%).

Conclusions:

• Early embryonic loss and aneuploidy formation are not directly related to mtDNA copy number.
• Spontaneous abortion cases exhibit a greater likelihood of harboring potentially pathogenic mtDNA mutations.
• Further research is needed to confirm if the accumulation of pathogenic mtDNA mutations causes early embryonic loss.