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.