MicroRNA-451 plays a role in murine embryo implantation through targeting Ankrd46, as implicated by a microarray-based analysis

Objective: To determine the potential microRNA (miRNA) regulators of embryo implantation, as a continuation of genomic and proteomic research. Design: Laboratory animal research. Setting: University hospital laboratory. Animal(s): Adult healthy female C57BL6/J mice (age 6-8 weeks, nonfertile, weighing 18-20 g each). Intervention(s): Female mice were mated naturally with fertile males to produce pregnancy. Luminal epithelium was collected by laser-capture microdissection during the implantation period. Mouse models of pseudopregnancy, delayed implantation, and artificial decidualization were established. Main outcome measure(s): The miRNA profile in luminal epithelium was clarified by microarray analysis and validated by real-time reverse transcription polymerase chain reaction (qRT-PCR) in a series of models. Target genes were predicted and confirmed by luciferase activity assay. The role of miRNA in implantation was examined by loss-of-function and gain-of-function of miRNA in vitro and in vivo. Result(s): A total of 29 and 15 miRNAs were up-and down-regulated, respectively, during the implantation period; 11 of these miRNAs were validated by qRT-PCR. The profile of miR-451 was clarified in a series of models. A dual-luciferase activity assay showed that Ankrd46 was a target gene of miR-451. Loss-of-function by LV-miR-451 sponge or miR-451 inhibitor led to a reduced number of embryo implantations, but had little effect on fertilization. Conclusion(s): miR-451 was specifically up-regulated during the implantation period, and it may play a major role in embryo implantation by targeting Ankrd46. (Fertil Steril (R) 2015; 103: 834-44. (C) 2015 by American Society for Reproductive Medicine.)