Impact of Cigarette Smoking on the Expression of Oxidative Stress-Related Genes in Cumulus Cells Retrieved from Healthy Women Undergoing IVF

Int J Mol Sci. 2021 Dec 5;22(23):13147. doi: 10.3390/ijms222313147.

Abstract

The female reproductive system represents a sensitive target of the harmful effects of cigarette smoke, with folliculogenesis as one of the ovarian processes most affected by this exposure. The aim of this study was to analyze the impact of tobacco smoking on expression of oxidative stress-related genes in cumulus cells (CCs) from smoking and non-smoking women undergoing IVF techniques. Real time PCR technology was used to analyze the gene expression profile of 88 oxidative stress genes enclosed in a 96-well plate array. Statistical significance was assessed by one-way ANOVA. The biological functions and networks/pathways of modulated genes were evidenced by ingenuity pathway analysis software. Promoter methylation analysis was performed by pyrosequencing. Our results showed a down-regulation of 24 genes and an up-regulation of 2 genes (IL6 and SOD2, respectively) involved in defense against oxidative damage, cell cycle regulation, as well as inflammation in CCs from smoking women. IL-6 lower promoter methylation was found in CCs of the smokers group. In conclusion, the disclosed overall downregulation suggests an oxidant-antioxidant imbalance in CCs triggered by cigarette smoking exposure. This evidence adds a piece to the puzzle of the molecular basis of female reproduction and could help underlay the importance of antioxidant treatments for smoking women undergoing IVF protocols.

Keywords: DNA methylation; IVF; cigarette smoke; cumulus cells; epigenetics; female reproduction; gene expression; infertility; oxidative stress.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cigarette Smoking / adverse effects*
  • Cumulus Cells / chemistry*
  • Cumulus Cells / drug effects
  • DNA Methylation
  • Female
  • Fertilization in Vitro
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks
  • Humans
  • Interleukin-6 / genetics*
  • Oxidative Stress / drug effects
  • Promoter Regions, Genetic
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Superoxide Dismutase / genetics*
  • Up-Regulation*

Substances

  • IL6 protein, human
  • Interleukin-6
  • Superoxide Dismutase
  • superoxide dismutase 2