Placenta-Specific miR-125b Overexpression Leads to Increased Rates of Pregnancy Loss in Mice

Int J Mol Sci. 2022 Jan 15;23(2):943. doi: 10.3390/ijms23020943.

Abstract

Pregnancy loss (PL) is one of the common complications that women can experience during pregnancy, with an occurrence rate of 1 to 5%. The potential causes of pregnancy loss are unclear, with no effective treatment modalities being available. It has been previously reported that the level of miR-125b was significantly increased in placentas of PL patients. However, the role of miR-125b in the development of PL still remains unknown. In the current study, an miR-125b placenta-specific over-expression model was constructed by lentiviral transfecting zona-free mouse embryos followed by embryo transfer. On gestation day 15, it was observed that the placenta was significantly smaller in the miR-125b placenta-specific overexpression group than the control group. Additionally, the abortion rate of the miR-125b placenta-specific overexpression group was markedly higher than in the control group. The blood vessel diameter was larger in the miR-125b-overexpressing specific placenta. In addition, miR-125b-overexpressing HTR8 and JEG3 cell lines were also generated to analyze the migration and invasion ability of trophoblasts. The results showed that miR-125b overexpression significantly suppressed the migration and invasion ability of HTR8 and JEG3 cells. Overall, our results demonstrated that miR-125b can affect embryo implantation through modulating placenta angiogenesis and trophoblast cell invasion capacity that can lead to PL.

Keywords: HTR8 cells; JEG3 cells; VEGF; angiogenesis; pregnancy loss.

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Animals
  • Case-Control Studies
  • Cell Line
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Organ Specificity
  • Placenta / chemistry*
  • Pregnancy
  • Up-Regulation*

Substances

  • MIRN125 microRNA, human
  • MicroRNAs