Virtual Presentation SRB Virtual Awards 2020

The influence of lipid-derived reactive carbonyl species on protein homeostasis and male reproductive health (#19)

Elizabeth Bromfield 1
  1. The University of Newcastle, Callaghan, NSW, Australia

Oxidative stress, caused by the over production of reactive oxygen and nitrogen species, is held as a key purveyor of cell death, dysfunction and tissue deterioration in almost every biological context. However, this paradigm has experienced a recent shift as research from our laboratory, and others, has demonstrated that cell life and death decisions are heavily influenced by lipid-derived envoys of stress termed reactive carbonyl species (RCS). These compounds are cytotoxic products of the oxidative breakdown of polyunsaturated fatty acids that cause widespread cellular damage through their ability to modify the DNA and protein content of cells. In the context of reproduction, the research of my team has demonstrated that protein homeostasis is particularly vulnerable to reactive carbonyl stress, whereby damage to the proteome by RCS results in severe consequences for male fertility. Moreover, by interrupting the lipoxygenase-lipid peroxidation pathway of germ cells and mature spermatozoa, we have developed a new strategy to prevent RCS-induced oxidative damage. This work is critical as RCS are now known to contribute to a failure of sperm-egg interaction, reproductive ageing, pregnancy loss and still birth. Additionally, RCS, contribute substantial losses to the breeding efficiency of stallions, and compromise assisted reproduction procedures that are critical to the efficient production of livestock in Australia.

This presentation will highlight the work conducted by my team to (1) understand how RCS disrupt protein homeostasis and cause cell death in developing male germ cells and (2) develop strategies to curb the production of RCS and improve male reproductive health. This work has important implications for improving equine sperm storage, enhancing our understanding of human male infertility and preventing and predicting the impacts of oxidative stress-induced cellular damage in male germ cells.