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RESEARCH ARTICLE

Causes and consequences of oxidative stress in spermatozoa

Robert John Aitken A D , Zamira Gibb A , Mark A. Baker A , Joel Drevet B and Parviz Gharagozloo C
+ Author Affiliations
- Author Affiliations

A Priority Research Centre in Reproductive Science and Hunter Medical Research Institute, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia.

B GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 BP80006, Aubière cedex, France.

C CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA.

D Corresponding author. Email: john.aitken@newcastle.edu.au

Reproduction, Fertility and Development 28(2) 1-10 https://doi.org/10.1071/RD15325
Published: 3 December 2015

Abstract

Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent.

Additional keywords: apoptosis, fertilizing potential, lipid peroxidation, male germ line, oxidative DNA damage, ROS generation.


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