Forced Suppression of let-7a-5p in Mouse Blastocysts Improves Implantation Rate

Background: Embryo implantation requires appropriate communication between the blastocyst and endometrium. Recurrent implantation failure is an essential component of assisted reproductive technology. Also, miRNAs-mediated gene expression impacts the implantation process, and the down-regulation of some miRs, such as mmu-let-7a, improves this process. In the present study, we evaluated the effect of let-7a forced-suppression on the mouse implantation rate. Methods: In total, 100 adult female mice and 10 adult male mice were included (Strain CD-1). We analysed the expression of let-7a and its potential mRNAs targets (Igf1, Il1a, Itgb3, and Tgfb1) in control, sham, and antagomir-treated blastocysts using quantitative reverse transcription PCR (qRT-PCR). The control and treated blastocysts were transferred to the 20 pseudopregnant mice so that the effect of let-7a suppression on the rate of implantation could be determined. Results: The expression level of let-7a in the treatment group was significantly down-regulated (P=0.001) In contrast, no significant expression changes were observed for let-7a or mRNAs targets when the sham and control groups were compared (P>0.05). In comparison to the controls, the antagomir-treated group exhibited significantly up-regulated expression levels of Igf1 (0.0167), Itgb3 (0.045), and Tgfb1 (0.0115). Additionally, the implantation rate was significantly higher in the treatment group (78%) than the control group (61%) (P=0.0098). Conclusion: We found that forced-suppression of mmu-let-7a-5p through successful transfection of Anti-miR leads to upregulation of downstream genes, Igf1, Itgb3, and Tgfb1, which directly involved in the trophoblast- endometrium attachment and improve the implantation rate.