Mmu-microRNA-200a overexpression leads to implantation defect by targeting phosphatase and tensin homolog in mouse uterus

Reprod Sci. 2013 Dec;20(12):1518-28. doi: 10.1177/1933719113488453. Epub 2013 May 20.

Abstract

Successful mouse embryo implantation requires a receptive uterus and an activated blastocyst. A large number of genes, cytokines, and other factors are involved in the process. MicroRNAs (miRNAs) regulate the expression of many genes, and previous studies have investigated the relationship between miRNA expression and embryo implantation. In this study, we show that mmu-microRNA-200a (mmu-miR-200a) is expressed in a spatiatemporal manner during implantation in mouse uterus and found that phosphatase and tensin homolog (PTEN), SON, and programmed cell death 4 (Pdcd4) are the target genes of mmu-miR-200a by bioinformatics analysis. In vitro gain and loss of function experiments confirm that PTEN, a critical gene for cell proliferation and apoptosis, is the target gene of mmu-miR-200a. Our experiments also show that injection of the uterine horn with mmu-miR-200a lentivirus leads to a decreased implantation rate. Collectively, our results suggest that mmu-miR-200a affects embryo implantation by regulating PTEN protein expression. Thus, clarifying the physiological functions of uterine miRNAs will help to elucidate the embryo implantation process and may even contribute to curing infertility and inventing new contraceptives.

Keywords: implantation; microRNA; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Embryo Implantation*
  • Female
  • Gene Expression Regulation, Developmental
  • Genetic Vectors
  • Lentivirus / genetics
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transfection
  • Up-Regulation
  • Uterus / enzymology*
  • Uterus / physiopathology

Substances

  • Apoptosis Regulatory Proteins
  • MicroRNAs
  • Mirn200 microRNA, mouse
  • Pdcd4 protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • PTEN Phosphohydrolase
  • Pten protein, mouse