Ferroptosis: A Novel Type of Cell Death in Male Reproduction

Genes (Basel). 2022 Dec 23;14(1):43. doi: 10.3390/genes14010043.

Abstract

Ferroptosis, an iron-dependent type of regulated cell death, is triggered by the accumulation of lethal lipid peroxides. Due to its potential in exploring disease progression and highly targeted therapies, it is still a widely discussed topic nowadays. In recent studies, it was found that ferroptosis was induced when testicular tissue was exposed to some high-risk factors, such as cadmium (Cd), busulfan, and smoking accompanied by a variety of reproductive damage characteristics, including changes in the specific morphology and ferroptosis-related features. In this literature-based review, we summarize the related mechanisms of ferroptosis and elaborate upon its relationship network in the male reproductive system in terms of three significant events: the abnormal iron metabolism, dysregulation of the Cyst(e)ine/GSH/GPX4 axis, and lipid peroxidation. It is meaningful to deeply explore the relationship between ferroptosis and the male reproductive system, which may provide suggestions regarding pristine therapeutic targets and novel drugs.

Keywords: GPX4; ferroptosis; iron metabolism; lipid peroxidation; male infertility; male reproduction.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Ferroptosis* / genetics
  • Humans
  • Iron / metabolism
  • Lipid Peroxidation
  • Male
  • Phospholipid Hydroperoxide Glutathione Peroxidase

Substances

  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Iron

Grants and funding

This research was funded by the Natural Science Foundation of Hunan Province (2020JJ5383, 2021JJ40365) and the Health Commission Foundation of Hunan Province (202104052273, 202102050927).