Exosomal miR-27 negatively regulates ROS production and promotes granulosa cells apoptosis by targeting SPRY2 in OHSS

J Cell Mol Med. 2021 Apr;25(8):3976-3990. doi: 10.1111/jcmm.16355. Epub 2021 Feb 27.

Abstract

Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous iatrogenic complications in controlled ovarian hyperstimulation (COH). The exact molecular mechanism that induces OHSS remains unclear. In recent years, accumulating evidence found that exosomal miRNAs participate in many diseases of reproductive system. However, the specific role of miRNAs, particularly the follicular fluid-derived exosomal miRNAs in OHSS remains controversial. To identify differentially expressed follicular fluid exosomal miRNAs from OHSS and non-OHSS patients, the analysis based on miRNA-sequence was conducted. The levels of 291 miRNAs were significantly differed in exosomes from OHSS patients compared with normal control, and exosomal miR-27 was one of the most significantly down-regulated miRNAs in the OHSS group. By using MiR-27 mimic, we found it could increase ROS stress and apoptosis by down-regulating the expression of p-ERK/Nrf2 pathway by negatively regulating SPRY2. These data demonstrate that exosomal miRNAs are differentially expressed in follicular fluid between patients with and without OHSS, and follicular fluid exosomal miR-27 may involve in the pathological process of OHSS development.

Keywords: OHSS; exosome; follicular fluid; miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis*
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Exosomes / genetics*
  • Female
  • Follicular Fluid / metabolism
  • Gene Expression Regulation
  • Granulosa Cells / metabolism
  • Granulosa Cells / pathology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics*
  • Ovarian Hyperstimulation Syndrome / genetics
  • Ovarian Hyperstimulation Syndrome / metabolism
  • Ovarian Hyperstimulation Syndrome / pathology*
  • Prognosis
  • Reactive Oxygen Species / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MIRN27 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Reactive Oxygen Species
  • SPRY2 protein, human