Molecular and Cellular Endocrinology 250 (2006) 70–79 The antioxidant glutathione peroxidase family and spermatozoa: A complex story Jo¨ el R. Drevet ∗ Universit´ e Blaise Pascal, CNRS UMR 6547 GEEM, 24 Avenue des Landais, 63177 Aubi` ere, France Abstract Oxidative damage is one threat spermatozoa have to face during epididymal maturation and storage. However, it is clear that reactive oxygen species (ROS) are also central for sperm physiology in processes such as sperm maturation and capacitation. It is therefore essential that there exists around sperm cells a fine balance between ROS production and recycling. To do so, sperm cells and epididymal epithelial cells rely on common enzymatic ROS scavengers such as superoxide dismutase (SOD), glutathione peroxidases (GPX) and catalase (CAT) as well as more specific types such as indoleamine dioxygenase (IDO). Among the catalytic triad (SOD/GPX/CAT), the glutathione peroxidase protein family occupies a peculiar position, since several GPX have been found to be present on and around epididymal transiting sperm cells. Here, we will review our present knowledge regarding GPX expression, presence and putative role(s) within the epididymis and on spermatozoa. Taking into account our recent findings regarding the epididymal expression of indoleamine dioxygenase in mouse we will also discuss how we think this superoxide anion recycling enzyme completes the complex ROS generation/recycling balance in this organ. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: GPX; Sperm maturation; Male genital tract; Epididymis 1. Introduction On one side, oxygen supports life for aerobic organisms in which oxidative metabolism is the principal source of energy. On the other side, oxygen consumption generates by-products, active forms of oxygen metabolites and peroxidized molecules, also called reactive oxygen species (ROS) that are dangerous for the cell. ROS are partially reduced forms of atmospheric oxy- gen (O 2 ). They typically result from the excitation of O 2 to form singlet oxygen (O 2 1 ) or from the transfer of one, two or three electrons to O 2 to form, respectively, a superoxide anion (O 2 •- ), hydrogen peroxide (H 2 O 2 ) or a hydroxyl radical (OH • ). There are many potential sources for ROS production in eukaryotic cells both within and outside the cell. In addition, environmental stresses can also cause an increase in ROS production leading to oxidative stress. In contrast to atmospheric O 2 , ROS may cause unrestricted oxidation of various cellular components, leading to free radical-mediated destruction of the cell. However, beside their noxious effects, ROS participate, in a more controlled man- ner, in physiological responses and early signaling pathways in response to various stimuli. ∗ Tel.: +33 4 73 40 74 13; fax: +33 4 73 40 70 42. E-mail address: joel.drevet@univ-bpclermont.fr. To counteract the noxious effects of ROS, cells use various non-enzymatic molecules (such as glutathione, thioredoxin and others thiol-containing molecules, as well as Vitamins [D, E and C] and several other small metabolites. To complete their antioxidant equipment, aerobic cells have also evolved spe- cific enzymatic ROS scavengers including superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) and glutathione peroxidases (GPX, EC 1.11.1.9) that work closely together. The SOD/CAT/GPX catalytic triad is quite ubiquitous and has been found in virtually all prokaryotic and eukaryotic aerobic organ- isms. Glutathione S-transferases (GST), thioredoxin peroxidases (TRX) and peroxiredoxins (PRX) complete the eukaryotic cell equipment to recycle ROS. Superoxide dismutase catalyzes the dismutation of the super- oxide anion (O 2 •- ) to produce hydrogen peroxide (H 2 O 2 ). Although it recycles the superoxide anion free radical, one can consider SOD more as a pro-oxidant since it converts a rather short-lived and confined molecule (O 2 •- ) into a quite stable and invasive one, H 2 O 2 . Moreover, taking into account the Fen- ton/Haberweiss coupled reactions, H 2 O 2 accumulation if not efficiently recycled, will lead to the appearance of the very aggressive hydroxyl radical (OH • ). The latter will attack any cell components, starting with lipids in membranes, proteins, carbohydrates as well as nucleic acids ultimately leading to cell death. To efficiently recycle hydrogen peroxide, two enzymatic 0303-7207/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2005.12.027