Hammond Elizabeth R, Shelling Andrew N, Cree Lynsey M
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand Fertility Associates, Greenlane, Auckland 1051, New Zealand
Hum Reprod. 2016 Aug;31(8):1653-61. doi: 10.1093/humrep/dew132. Epub 2016 Jun 6.
The ability to screen embryos for aneuploidy or inherited disorders in a minimally invasive manner may represent a major advancement for the future of embryo viability assessment. Recent studies have demonstrated that both blastocoele fluid and embryo culture medium contain genetic material, which can be isolated and subjected to downstream genetic analysis. The blastocoele fluid may represent an alternative source of nuclear DNA for aneuploidy testing, although the degree to which the isolated genetic material is solely representative of the developing embryo is currently unclear. In addition to nuclear DNA, mitochondrial DNA (mtDNA) can be detected in the embryo culture medium. Currently, the origin of this nuclear and mtDNA has not been fully evaluated and there are several potential sources of contamination that may contribute to the genetic material detected in the culture medium. There is however evidence that the mtDNA content of the culture medium is related to embryo fragmentation levels and its presence is predictive of blastulation, indicating that embryo development may influence the levels of genetic material detected. If the levels of genetic material are strongly related to aspects of embryo quality, then this may be a novel biomarker of embryo viability. If the genetic material does have an embryo origin, the mechanisms by which DNA may be released into the blastocoele fluid and embryo culture medium are unknown, although apoptosis may play a role. While the presence of this genetic material is an exciting discovery, the DNA in the blastocoele fluid and embryo culture medium appears to be of low yield and integrity, which makes it challenging to study. Further research aimed at assessing the methodologies used for both isolating and analysing this genetic material, as well as tracing its origin, are needed in order to evaluate its potential for clinical use. Should such methodologies prove to be routinely successful and the DNA recovered demonstrated to be embryonic in origin, then they may be used in a minimally invasive and less technical methodology for genetic analysis and embryo viability assessment than those currently available.
以微创方式筛查胚胎非整倍体或遗传性疾病的能力可能代表着胚胎活力评估未来的一项重大进展。最近的研究表明，囊胚腔液和胚胎培养基中都含有遗传物质，这些遗传物质可以被分离出来并进行下游基因分析。囊胚腔液可能是用于非整倍体检测的核DNA的另一种来源，尽管目前尚不清楚分离出的遗传物质在多大程度上仅代表发育中的胚胎。除了核DNA外，还可以在胚胎培养基中检测到线粒体DNA（mtDNA）。目前，这种核DNA和mtDNA的来源尚未得到充分评估，并且存在几种潜在的污染源，可能导致在培养基中检测到遗传物质。然而，有证据表明培养基中的mtDNA含量与胚胎碎片化水平有关，其存在可预测囊胚形成，这表明胚胎发育可能会影响检测到的遗传物质水平。如果遗传物质的水平与胚胎质量的各个方面密切相关，那么这可能是一种新的胚胎活力生物标志物。如果遗传物质确实来源于胚胎，那么DNA可能释放到囊胚腔液和胚胎培养基中的机制尚不清楚，尽管细胞凋亡可能起作用。虽然这种遗传物质的存在是一个令人兴奋的发现，但囊胚腔液和胚胎培养基中的DNA产量和完整性似乎较低，这使得研究具有挑战性。需要进一步开展研究，以评估用于分离和分析这种遗传物质以及追踪其来源的方法，以便评估其临床应用潜力。如果这些方法被证明常规成功，并且回收的DNA被证明来源于胚胎，那么它们可能会被用于一种比目前可用方法更微创、技术要求更低的基因分析和胚胎活力评估方法。
