Effects of Fullerenol Nanoparticles on Rat Oocyte Meiosis Resumption

Int J Mol Sci. 2018 Mar 1;19(3):699. doi: 10.3390/ijms19030699.

Abstract

The excellent biocompatibility and biological effects of fullerenol and its derivatives make their biomedical application promising. The potential effects of fullerenol in mammals have been extensively studied, but little is known about its effects on female reproduction. Using canonical oocyte-granulosa cell complexes (OGCs) in vitro maturation culture model, we investigated the effect of fullerenol on the first oocyte meiotic resumption. In the surrounding granulosa cells, fullerenol nanoparticles occluded the extracellular domain of the epidermal growth factor receptor (EGFR) to reduce EGFR-ligand binding and subsequent extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation, which involved the regulation of connexin 43 (CX43) expression and internalization. Downregulation of CX43 expression and the retraction of transzonal projections (TZPs) interrupted the gap junction channel and TZPs based mass transportation. This effect decreased cyclic adenosine monophosphate (cAMP) levels in the oocyte and thereby accelerated rat oocyte meiosis resumption. Moreover, perinuclear distribution of CX43 and EGFR was observed in granulosa cells, which could further exacerbate the effects. Fullerenol nanoparticles interfered with the strict process of oocyte meiosis resumption, which likely reduced the oocyte quality.

Keywords: EGFR/ERK1/2; fullerenol; gap junction; granulosa cells; oocyte meiosis resumption.

MeSH terms

  • Animals
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Cyclic AMP
  • ErbB Receptors / metabolism
  • Female
  • Fullerenes / chemistry
  • Fullerenes / pharmacology*
  • Gap Junctions / metabolism
  • Gene Expression Regulation / drug effects
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Meiosis / drug effects*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nanoparticles*
  • Oocytes / metabolism*
  • Protein Binding
  • Protein Transport / drug effects
  • Rats
  • Signal Transduction / drug effects

Substances

  • Connexin 43
  • Fullerenes
  • fullerenol
  • Cyclic AMP
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3