Purpose

To explore the relationship between mitochondrial DNA quantity and heteroplasmy and early embryonic loss.

Methods

A total of 150 villous samples from patients with spontaneous abortion (SA, n = 75) or induced abortion (IA, n = 75) were collected. qPCR and next-generation sequencing (NGS) were used to test mitochondrial DNA quantity and heteroplasmy. Missense mutations with a CADD score > 15 and heteroplasmy ≥ 70% were defined as potentially pathogenic mutations.

Results

With respect to mitochondrial DNA 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). 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.

中文翻译：

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深度测序表明，潜在致病性 mtDNA 突变的积累而不是 mtDNA 拷贝数可能与早期胚胎丢失有关。

目的

探讨线粒体DNA数量与异质性和早期胚胎丢失之间的关系。

方法

总共收集了150 个自然流产 (SA, n = 75) 或人工流产 (IA, n = 75) 患者的绒毛样本。qPCR和下一代测序（NGS）用于测试线粒体DNA数量和异质性。CADD 评分 > 15 且异质性≥ 70% 的错义突变被定义为潜在致病突变。

结果

就线粒体 DNA 拷贝数而言，SA 组和 IA 组之间（中位数 (IQR)，566 (397–791) 与 614 (457–739)；P = 0.768）或整倍体和非整倍体之间没有显着差异组（中位数 (IQR)，516 (345–730) 对比 599 (423–839)；P = 0.107）。使用逻辑回归分析，mtDNA 拷贝数与自然流产无关（P = 0.196，95% CI 1.000–1.001）。此外，与IA组（54.7%，41/75；P < 0.05）相比，SA组的绒毛膜绒毛中存在可能致病性mtDNA突变的患者更多（70.7%，53/75）。然而，整倍体组（80%，24/30）和非整倍体组（64.4%，29/45；p = 0.147）之间没有统计学差异。

结论

早期胚胎丢失和非整倍体的形成与线粒体DNA拷贝数无关。自然流产患者的线粒体DNA更有可能存在致病性突变，这可能有助于纯化致病性线粒体DNA。然而，这些潜在致病性 mtDNA 突变的积累是否导致早期胚胎丢失还需要进一步研究。