MicroRNA expression and regulation in the uterus during embryo implantation in rat

FEBS J. 2014 Apr;281(7):1872-91. doi: 10.1111/febs.12751. Epub 2014 Mar 7.

Abstract

Embryo implantation is a complex initial step in establishment of a successful pregnancy. Many mRNAs have been shown to be differentially expressed in the rat uterus during embryo implantation. However, the expression profiles of microRNAs (miRNAs), a key post-transcriptional regulator of gene expression, in the rat uterus between the pre-receptive and receptive phases are still unknown. Here, an miRNA microarray was used to examine differential expression of miRNAs in the rat uterus between the pre-receptive and receptive phases. Twenty-eight miRNAs were up-regulated and 29 miRNAs were down-regulated at least twofold during the receptive phase in rat uterus; these results were confirmed by Northern blotting. miR-29a was only highly expressed in rat uterus during the implantation period, and activation of delayed implantation and artificial decidualization enhanced the miR-29a level. Further investigation revealed that both the pro-apoptotic factor genes Bak1 and Bmf and the anti-apoptotic factor gene Bcl-w are targets of miR-29a. There was weak binding between miR-29a and the 3' UTR of the anti-apoptotic factor gene Mcl1. Over-expression of miR-29a inhibited the late apoptosis of endometrial stromal cells, which may be due to the stronger binding capacity between miR-29a and the 3' UTR of pro-apoptotic factors than that between miR-29a and the 3' UTR of anti-apoptotic factors. Collectively, miR-29a plays an important role during embryo implantation by regulating both pro-apoptotic and anti-apoptotic factors. miR-29a may predominantly bind pro-apoptotic factors, leading to inhibition of cell apoptosis.

Keywords: Bcl-2 family; embryo implantation; miR-29a; miRNAs; rat uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis
  • Embryo Implantation*
  • Endometrium / metabolism*
  • Female
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Bak1 protein, rat
  • Bcl2l2 protein, rat
  • Bmf protein, rat
  • MIRN29 microRNA, rat
  • Mcl1 protein, rat
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein