Evidence for the Autocrine Induction of Capacitation of Mammalian Spermatozoa

Abstract

Mammalian spermatozoa require a maturational event after ejaculation that allows them to acquire the capacity for fertilization. This process, known as capacitation, occurs spontaneously in simple defined medium implicating a potential role of autocrine induction. This study shows that the ether phospholipid 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF) meets the criteria for an autocrine mediator of capacitation. Sperm released PAF after their dilution into capacitation medium and expressed a receptor for PAF on their membranes. PAF stimulated changes in the motility of sperm and enhanced fertilization in vitro. These actions were inhibited by a PAF receptor antagonist (UR-12519) and by extracellular recombinant PAF:acetylhydrolase (an enzyme that degrades PAF to a biologically inert form). Seminal plasma contained an acid-labile PAF:acetylhydrolase, whereas capacitation was inhibited by an acid-labile factor within seminal plasma, implicating this factor as a potential decapacitation factor within seminal plasma. Sperm from a PAF receptor knock-out mouse strain failed to express the receptor and displayed a significantly (p < 0.01) reduced rate of capacitation, as assessed by the spontaneous onset of the acrosome reaction in vitro. When used for in vitro fertilization, sperm from PAF receptor knock-out mice gave a significantly lower rate of fertilization (21.5%) than did wild-type sperm (66.7%). The study shows for the first time the operation of an autocrine loop that induces capacitation in sperm in vitro and shows that this loop acts in concert with other mediators of capacitation to promote efficient fertilization.

FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

“…The regulation of global sperm tyrosine phosphorylation associated with capacitation is a complex process that probably involves input from several signaling pathways including the MAPK pathway, PKA, A1 adenosine receptor, and the platelet activating factor (PAF) receptor signaling (de Lamirande and Gagnon, 2002;Luconi et al, 1998;Minelli et al, 2004;Muguruma and Johnston, 1997;Roudebush et al, 2005;Wu et al, 2001). It is absolutely dependent upon cholesterol efflux (and an associated increase in membrane fluidity), bicarbonate and Ca 2+ influxes (Carlson et al, 2003;Davis and Gergely, 1979;Gadella and Harrison, 2000;Ho and Suarez, 2001).…”

Male Mice That Do Not Express Group VIA Phospholipase A2 Produce Spermatozoa with Impaired Motility and Have Greatly Reduced Fertility

“…A PLA 2 is activated during induction of the acrosomal reaction by zona pellucida and releases arachidonic acid and LPC from spermatozoa membrane phospholipids (46). LPC also induces the acrosome reaction in spermatozoa (30,32), and one species of LPC (2-lysoplasmanylcholine) is the precursor of the platelet-activating factor, which is produced by spermatozoa and is an autocrine inducer of capacitation (47).…”

Current Concepts of Molecular Events During Bovine and Porcine Spermatozoa Capacitation

“…As described above, PAF may be involved in autocrine activation of capacitation. Seminal plasma contains PAF-AH which is responsible for the inactivation of PAF [Odeh et al 2003;Wu et al 2001]. The removal of seminal plasma results in the removal of PAF-AH allowing the spermatozoon to release PAF without its degradation.…”

“…PAF has been discovered in bovine, porcine and other species' spermatozoa and female reproductive tracts and a receptor for PAF is expressed on the sperm plasma membrane [Odeh et al 2003]. During capacitation, spermatozoa release PAF in the presence of albumin [Wu et al 2001] which may contribute to increased membrane fluidity [Yamano et al 2004]. A model for PAF action involves increased intracellular calcium concentrations that cause PAF release from the spermatozoon.…”

“…The released PAF then binds extracellular albumin. Once a threshold concentration of PAF-albumin complexes are formed, PAF is released and binds to PAF receptors on the sperm plasma membrane activating capacitation-related signal transduction pathways [Wu et al 2001]. The addition of synthetic PAF to equine spermatozoa induced capacitation and enhanced motility as assayed with a computer automated motility analyzer [Odeh et al 2003]; correspondingly, spermatozoa from PAF receptor knock-out mice had a decreased rate of capacitation [Wu et al 2001].…”