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调整后的人胚胎线粒体 DNA 定量可能不适宜作为着床潜能的生物标志物。

Adjusted mitochondrial DNA quantification in human embryos may not be applicable as a biomarker of implantation potential.

机构信息

Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.

Division of Infertility, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan.

出版信息

J Assist Reprod Genet. 2019 Sep;36(9):1855-1865. doi: 10.1007/s10815-019-01542-6. Epub 2019 Aug 28.

Abstract

OBJECTIVE

To evaluate the feasibility of adjusted mitochondrial DNA quantification in human embryos as a biomarker for implantation potential.

DESIGN

Double-blind, observational, prospective analysis of an Asian population in a single university-affiliated in vitro fertilization center. A total of 1617 embryos derived from 380 infertile couples were collected. The DNA from blastomere biopsy (n = 99) or trophectoderm biopsy (n = 1518) were analyzed with next-generation sequencing.

RESULTS

The adjusted mtDNA quantification followed a non-normal distribution in both types of the embryos. When stratified by ploidy status, the adjusted mtDNA quantification was significantly higher in aneuploid trophectoderm than in euploid cells, but not in blastomeres. The adjusted mtDNA quantification of embryos showed significant but very weak positive correlation in total trophectoderm cells with maternal age (Spearman's correlation, r = 0.095, p = 0.0028) but neither in blastomeres nor stratified by ploidy status. The median adjusted mtDNA quantification was also significantly higher in aneuploid blastocysts than in euploid ones while corrected with embryo morphology. Viable embryos did not contain significantly different quantities of adjusted mtDNA compared with nonviable embryos (implanted n = 103, non-implanted n = 164; median 0.00097 vs. 0.00088, p = 0.21) in 267 transferred blastocysts.

CONCLUSION

Quantification of adjusted mitochondria DNA in human embryos was significantly lower in euploid blastocysts than in aneuploid blastocysts. However, no statistically significant differences regarding implantation outcome were evident. To our best knowledge, this study provides the largest scale and the first correlation data between mitochondria copy number and human embryo implantation potential in Asians.

摘要

目的

评估调整后的线粒体 DNA 定量分析在人类胚胎中的可行性,作为胚胎着床潜能的生物标志物。

设计

在一家大学附属的体外受精中心进行的亚洲人群的双盲、观察性、前瞻性分析。共收集了 380 对不孕夫妇的 1617 个胚胎。通过下一代测序分析卵裂球活检(n=99)或滋养外胚层活检(n=1518)的 DNA。

结果

两种胚胎的调整后 mtDNA 定量均呈现非正态分布。当按倍性状态分层时,非整倍体滋养外胚层的调整后 mtDNA 定量明显高于整倍体细胞,但卵裂球中并非如此。总滋养外胚层细胞的调整后 mtDNA 定量与母亲年龄呈显著但非常弱的正相关(Spearman 相关,r=0.095,p=0.0028),但卵裂球中无此相关性,且与倍性状态无关。在纠正胚胎形态后,非整倍体囊胚的调整后 mtDNA 中位数也明显高于整倍体囊胚。与非可植入胚胎相比,可植入胚胎中调整后的 mtDNA 含量没有显著差异(移植囊胚 267 个,可植入 n=103,非可植入 n=164;中位数 0.00097 与 0.00088,p=0.21)。

结论

整倍体囊胚中的调整后 mtDNA 定量明显低于非整倍体囊胚。然而,在植入结局方面没有明显的统计学差异。据我们所知,这项研究提供了亚洲人群中线粒体拷贝数与人类胚胎着床潜能之间最大规模和首次相关性数据。

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mtDNA dynamics between cleavage-stage embryos and blastocysts.卵裂期胚胎和囊胚之间的 mtDNA 动力学。
J Assist Reprod Genet. 2019 Sep;36(9):1867-1875. doi: 10.1007/s10815-019-01544-4. Epub 2019 Aug 7.

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The International Glossary on Infertility and Fertility Care, 2017.《国际不孕不育和生育保健词汇表》,2017 年。
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