title: Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice.
abstract: The mammalian epididymis provides sperm with an environment that promotes their maturation and protects them from external stresses. For example, it harbors an array of antioxidants, including non-conventional glutathione peroxidase 5 (GPX5), to protect them from oxidative stress. To explore the role of GPX5 in the epididymis, we generated mice that lack epididymal expression of the enzyme. Histological analyses of Gpx5-/- epididymides and sperm cells revealed no obvious defects. Furthermore, there were no apparent differences in the fertilization rate of sexually mature Gpx5-/- male mice compared with WT male mice. However, a higher incidence of miscarriages and developmental defects were observed when WT female mice were mated with Gpx5-deficient males over 1 year old compared with WT males of the same age. Flow cytometric analysis of spermatozoa recovered from Gpx5-null and WT male mice revealed that sperm DNA compaction was substantially lower in the cauda epididymides of Gpx5-null animals and that they suffered from DNA oxidative attacks. Real-time PCR analysis of enzymatic scavengers expressed in the mouse epididymis indicated that the cauda epididymidis epithelium of Gpx5-null male mice mounted an antioxidant response to cope with an excess of ROS. These observations suggest that GPX5 is a potent antioxidant scavenger in the luminal compartment of the mouse cauda epididymidis that protects spermatozoa from oxidative injuries that could compromise their integrity and, consequently, embryo viability.
authors: Epididymis & Sperm Maturation, GReD, CNRS UMR 6247, INSERM U931, Clermont Université, Aubière, France.
authors: Eléonore
authors: E
authors: Chabory
authors: Christelle
authors: C
authors: Damon
authors: Alain
authors: A
authors: Lenoir
authors: Gary
authors: G
authors: Kauselmann
authors: Hedrun
authors: H
authors: Kern
authors: Branko
authors: B
authors: Zevnik
authors: Catherine
authors: C
authors: Garrel
authors: Fabrice
authors: F
authors: Saez
authors: Rémi
authors: R
authors: Cadet
authors: Joelle
authors: J
authors: Henry-Berger
authors: Michael
authors: M
authors: Schoor
authors: Ulrich
authors: U
authors: Gottwald
authors: Ursula
authors: U
authors: Habenicht
authors: Joël R
authors: JR
authors: Drevet
authors: Patrick
authors: P
authors: Vernet
mesh_terms: D000818:Animals; D004249:DNA Damage; D053938:DNA Fragmentation; D004822:Epididymis / Q000201:enzymology*; D005260:Female; D005298:Fertility; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase