title: Progesterone-induced Acrosome Exocytosis Requires Sequential Involvement of Calcium-independent Phospholipase A2β (iPLA2β) and Group X Secreted Phospholipase A2 (sPLA2).
abstract: Phospholipase A2 (PLA2) activity has been shown to be involved in the sperm acrosome reaction (AR), but the molecular identity of PLA2 isoforms has remained elusive. Here, we have tested the role of two intracellular (iPLA2β and cytosolic PLA2α) and one secreted (group X) PLA2s in spontaneous and progesterone (P4)-induced AR by using a set of specific inhibitors and knock-out mice. iPLA2β is critical for spontaneous AR, whereas both iPLA2β and group X secreted PLA2 are involved in P4-induced AR. Cytosolic PLA2α is dispensable in both types of AR. P4-induced AR spreads over 30 min in the mouse, and kinetic analyses suggest the presence of different sperm subpopulations, using distinct PLA2 pathways to achieve AR. At low P4 concentration (2 μm), sperm undergoing early AR (0-5 min post-P4) rely on iPLA2β, whereas sperm undergoing late AR (20-30 min post-P4) rely on group X secreted PLA2. Moreover, the role of PLA2s in AR depends on P4 concentration, with the PLA2s being key actors at low physiological P4 concentrations (≤2 μm) but not at higher P4 concentrations (~10 μm).
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Abi Nahed
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martinez
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Escoffier
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Yassine
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Karaouzène
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France.
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Hograindleur
authors.affiliation: the Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.affiliation: the Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kokotos
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France, the Centre Hospitalier Universitaire de Grenoble, Unité Fonctionnelle de Biochimie et Génétique Moléculaire, Grenoble F-38000, France.
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Ray
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France, the Centre Hospitalier Universitaire de Grenoble, Plate-forme de Radioanalyse, IBP, CS10217, Grenoble F-38000, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Bottari
authors.affiliation: the Université de Nice-Sophia Antipolis, Valbonne 06560, France, the Centre Hospitalier Universitaire de Grenoble, Centre d'AMP-CECOS, CS1021, Grenoble F-38000, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France, the Centre Hospitalier Universitaire de Grenoble, Centre d'AMP-CECOS, CS1021, Grenoble F-38000, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Hennebicq
authors.affiliation: From the Université Grenoble Alpes, F-38000 Grenoble, France, the Institut Albert Bonniot, INSERM U823, La Tronche F-38700, France, Christophe.arnoult@ujf-grenoble.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Arnoult
mesh_terms: D000177:Acrosome / Q000201:enzymology*; D020101:Acrosome Reaction / Q000187:drug effects*; D000818:Animals; D005089:Exocytosis / Q000187:drug effects*; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D054509:Group X Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011374:Progesterone; D054522:Group VI Phospholipases A2; D054509:Group X Phospholipases A2; C516476:Pla2g6 protein, mouse
keywords: acrosome; exocytosis; iPLA2β; phospholipase A; progesterone; secreted PLA2; sperm; spermatogenesis