Department of Gynecologic Endocrinology and Fertility Disorders at Heidelberg University Women's HospitalHeidelberg, Germany
Saarland UniversityUniversity Hospital, Saarbrücken, Germany.
Reproduction. 2017 Dec;154(6):799-805. doi: 10.1530/REP-17-0396. Epub 2017 Sep 29.
Main goal of this study is to detect the possible alterations in microRNA (miRNA) expression and the pathway targeted in plasma at the time of embryo transfer and pregnancy testing dependent on the assisted reproductive treatment (ART) outcome after ovarian hyperstimulation for fertilization. Changes in miRNA expression in plasma of women, who became pregnant ( = 6) vs women who failed implantation ( = 6) following day 5 embryo transfer (ET), were investigated at the day of ET and pregnancy testing (PT). Protein expression to validate the finding was performed with a sample size of = 20 (10 per group) using enzyme-linked immunosorbent assay. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DIANA-miRPath, v3.0 software based on predicted targets by DIANA-microT-CDS. 4 miRNAs could be identified as possible biomarkers for implantation success. The 11 miRNAs showing the highest significant alterations were all associated with the regulation of WNT3 and WNT7a. While WNT7a presented with a significant decrease between ET and PT in case of ongoing pregnancy, women with implantation failure showed unaltered concentrations. WNT3 presented with a significant decrease in both groups. However, the loss of WNT3 between ET and PT was significantly higher in patients who became pregnant. Main limitation of this prospective study is its small sample size, defining it as a pilot analysis. To conclude, we could demonstrate a significant change in miRNA profile dependent on the ART outcome affecting Wnt pathway. Our findings indicate a possible prospective use of miRNA as biomarkers for implantation success.
本研究的主要目的是检测在接受卵巢刺激以进行受精后，胚胎移植和妊娠检测时，与辅助生殖治疗（ART）结果相关的血浆中微小 RNA（miRNA）表达和靶向途径的可能变化。对接受第 5 天胚胎移植（ET）后妊娠（ = 6）和着床失败（ = 6）的女性，在 ET 日和妊娠检测（PT）日检测血浆中 miRNA 表达的变化。使用酶联免疫吸附试验（ELISA）对 20 个样本（每组 10 个）进行蛋白表达验证。通过 DIANA-microT-CDS 预测的靶标，使用 DIANA-miRPath，v3.0 软件进行京都基因与基因组百科全书（KEGG）途径富集分析。鉴定出 4 个 miRNA 作为着床成功的可能生物标志物。显示最高显著变化的 11 个 miRNA 均与 WNT3 和 WNT7a 的调节有关。在妊娠持续的情况下，WNT7a 在 ET 和 PT 之间的浓度显著降低，而着床失败的女性浓度不变。WNT3 在两组中均显著降低。然而，在妊娠的患者中，WNT3 在 ET 和 PT 之间的丢失明显更高。本前瞻性研究的主要局限性是样本量小，定义为初步分析。总之，我们可以证明 miRNA 谱随 ART 结果的显著变化，影响 Wnt 途径。我们的研究结果表明，miRNA 作为着床成功的生物标志物具有潜在的前瞻性。
