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Originally published In Press as doi:10.1074/jbc.M103107200 on May 11, 2001

J. Biol. Chem., Vol. 276, Issue 29, 26962-26968, July 20, 2001
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Evidence for the Autocrine Induction of Capacitation of Mammalian Spermatozoa*

Cuigi WuDagger §, Tomas StojanovDagger §, Omar ChamiDagger , Santoshi Ishii||, Takao Shimuzu||, Aiging LiDagger , and Chris O'Neill**

From the Dagger  Human Reproduction Unit, Department of Physiology, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia, || CREST of Japan Science and Technology Corporation, Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

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.

* This work was supported by a grant from the Australian National Health and Medical Research Council.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

Current address: Dept. of Histology and Embryology, Medical College, Qingdao University, China.

** To whom all correspondence should be addressed: Human Reproduction Unit, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. Tel.: 61 2 9926 7148; Fax: 61 2 9926 6343; E-mail chriso@med.usyd.edu.au.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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