A Study On The Relationship Between Mitochondrial DNA Quantity And Heteroplasmy And Early Embryonic Loss

Purpose: To explore the relationship between mitochondrialDNA quantity and heteroplasmy and early embryonic loss.Methods: The villous samples were collected from patients with spontaneous abortion(SA,n=75)or induced abortion(IA,n=75).qPCR and next-generation sequencing(NGS)were used to test mitochondrialDNA quantity and heteroplasmy.Missense mutations with a CADD score >15 and heteroplasmy≥70% were defined as potentially pathogenic mutations.Results: With respect to mitochondrialDNA copy numbers,there was no significant difference between the SA and IA groups(median [IQR],566 [397–791] vs.614 [457–739];P=0.768)or between the euploid and aneuploid groups(median [IQR],516 [345–730] vs.599 [423–839];P=0.107).mtDNA copy numbers were not associated with spontaneous abortion using logistic regression analysis(P=0.196,95% CI: 1.000-1.001).Patients in SA group(mean±sd,3.29±2.45)harbored more mtDNA mutations in heteroplasmy in 1%-10% compared with the IA group(mean±sd,2.36±1.47;P<0.05).In addition,more patients harbored possibly pathogenic mtDNA mutations in their chorionic villi in the SA group(70.7%,53/75)compared with the IA group(54.7%,41/75;P<0.05).However,there was no statistical difference between the euploid(80%,24/30)and aneuploid groups(64.4%,29/45;P=0.147).Conclusion: Early embryonic loss and the formation of aneuploidy were not related to mtDNA copy number.Patients with spontaneous abortion were more likely to have possibly pathogenic mutations in their mtDNA,and this may assist in purifying pathogenic mtDNA.However,whether the accumulation of these potentially morbific mtDNA mutations caused early embryonic loss requires further investigation.