Mammalian spermatozoa require a maturational event after ejaculation that a
llows them to acquire the capacity for fertilization. This process, known a
s capacitation, occurs spontaneously in simple defined medium implicating a
potential role of autocrine induction. This study shows that the ether pho
spholipid 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine (PAF) meets the c
riteria for an autocrine mediator of capacitation. Sperm released PAF after
their dilution into capacitation medium and expressed a receptor for PAF o
n their membranes. PAF stimulated changes in the motility of sperm and enha
nced 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 in
hibited by an acid-labile factor within seminal plasma, implicating this fa
ctor as a potential decapacitation factor within seminal plasma. Sperm from
a PAF receptor knock-out mouse strain failed to express the receptor and d
isplayed a significantly (p < 0.01) reduced rate of capacitation, as assess
ed by the spontaneous onset of the acrosome reaction in vitro. When used fo
r in vitro fertilization, sperm from PAF receptor knock-out mice gave a sig
nificantly 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 Poop
that induces capacitation in sperm in vitro and shows that this loop acts
in concert with other mediators of capacitation to promote efficient fertil
ization.