Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway

Abstract

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.

Identification of the master sex determining gene in Northern pike (Esox lucius) reveals restricted sex chromosome differentiation

“…Since the discovery of dmrt1bY in the Japanese rice fish [28,29], the first identified teleost master sex determination gene, studies in teleosts have unveiled a dozen novel genes as master regulators for sex determination [14–16,27]. Interestingly, many of these master sex determining genes belong to the TGF- β superfamily.…”

“…Beside this remarkable dynamic of sex determination systems, the rapid turnover of sex chromosomes in teleosts provides many opportunities to examine sex chromosome pairs at different stages of differentiation. Finally, recent studies on fish sex determination have revealed a dozen new master sex determining (MSD) genes [14,16,27], providing additional insight to the forces driving the turnover of SD systems and the formation of sex chromosomes.…”

Wingless ligands and beta‐catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta‐catenin pathway at the embryo–uterine interface

“…Beta‐catenin and Wnt7a mRNAs are upregulated and Wnt3 is downregulated in the transition from the proestrus to the estrus stage, and the opposite relationship occurs when switching from metaestrus to diestrus, suggesting that transition stages to estrus and diestrus may be decisive for the Wnt signaling pathway. Although the precise mechanism involving the Wnt7a and Wnt3 regulation remains unclear, it may be responsive to steroid hormones (Rider et al, 2006, 2016) and microRNAs (miRNAs) since the 11 miRNAs showing the highest significant alterations were all associated with the regulation of Wnt3 and Wnt7a (Freis et al, 2017).…”

“…showing the highest significant alterations were all associated with the regulation of Wnt3 and Wnt7a (Freis et al, 2017).…”

The role of microRNAs in human embryo implantation: a review

“…In this review, we reviewed work analyzing the potential of miRNA isolated from blastocyst and endometrium in predicting the window of implantation or likelihood of successful implantation. Freis et al explored microRNA in serum during the window of implantation and found four miRNAs that could be possible biomarkers for implantation success [57]. However, studies profiling miRNA expression show inconsistent results due to the complexity of miRNA signaling, its rapid variation with time, and variation between individuals.…”