Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition

Int J Mol Sci. 2023 Oct 13;24(20):15149. doi: 10.3390/ijms242015149.

Abstract

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

Keywords: embryo implantation; endometrial receptivity; exosomal miRNA; exosome; miR-205-5p/ZEB1/E-cadherin axis.

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Embryo Implantation / genetics
  • Endometrium / metabolism
  • Female
  • Humans
  • Infertility, Female* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Cadherins
  • MicroRNAs
  • MIRN205 microRNA, human
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • CDH1 protein, human