Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Causes and consequences of oxidative damage in the male germ line (#307)

Geoffry N De Iuliis 1
  1. The University of Newcastle, CALLAGHAN, NSW, Australia

Many sub-fertile men can produce the numbers of sperm required to normally achieve natural fertilisation, but nevertheless, must seek recourse to assisted reproductive technologies. For these men, where the cause of their sub-fertility is deemed idiopathic, the functionality of their spermatozoa must be somehow compromised. Despite the relatively poor understanding of the underlying origins of many sperm defects, discoveries in the last decade have implicated oxidative stress as a major contributor. There is now a clear need to identify the origins of this stressor and based on this knowledge, to develop therapeutic strategies for these men. The mature spermatozoon is exceedingly vulnerable to oxidative stress, owing to inadequacies in their ability to quench reactive oxygen species (ROS). The ensuing elevation of ROS levels not only limits the fertilising potential of these cells but also leads to nuclear and potentially epigenetic damage. One of the most direct incursions resulting from oxidative stress in spermatozoa is the formation of the DNA adduct, 8-hydroxyguanosine (8-OHG), but investigations of defective sperm function in our species has identified other cellular targets, including electron transport chain proteins and key molecules that mediate oocyte-recognition. We have used several approaches to study the onset and impact of oxidative stress with the aim of identifying the molecular mechanisms that underpin sperm dysfunction. ROS generation leads to an oxidative stress cascade which results in the perturbation of key elements that are otherwise critical for defining fertilisation capacity. This disruption is achieved by the products of oxidative chemistry within spermatozoa, which can modify a subset of key sperm proteins. We are now gaining better insights into the mechanisms of oxidative damage and with this foundation, are be better placed to aid in the development of targeted therapeutics that aim to minimise both the genetic and cellular damage of the male gamete.