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Sperm from Mice Genetically Deficient for the PCSK4 Proteinase Exhibit Accelerated Capacitation, Precocious Acrosome Reaction, Reduced Binding to Egg Zona Pellucida, and Impaired Fertilizing Ability¹

Ottawa Health Research Institute,⁴ Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9 Cancer Research—Unit F2—Major Diseases DG Research,⁵ European Commission CDMA 2/47, B-1049 Brussels, Belgium Department of Pathology and Cell Biology,⁶ Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada H3T 1J4

ABSTRACT

The gene for proprotein convertase subtilisin/kexin-like 4 (PCSK4, previously known as PC4) is primarily transcribed in testicular spermatogenic cells. Its inactivation in mouse causes severe male subfertility. To better understand the reproductive function of PCSK4, we examined its subcellular localization in the testicular epithelium via immunohistochemistry, and on intact sperm via indirect immunofluorescence and immunoelectron microscopy. PCSK4 was detected in the acrosomal granules of round spermatids, in the acrosomal ridges of elongated spermatids, and on the sperm plasma membrane overlying the acrosome. We also investigated PCSK4 relevance for sperm acquisition of fertilizing ability by comparing wild-type and PCSK4-null sperm for their abilities in capacitation, acrosome reaction, and egg binding in vitro. PCSK4-null sperm underwent capacitation at a faster rate; they were induced to acrosome react by lower concentrations of zona pellucida; and their egg-binding ability was only half that of wild-type sperm. These sperm physiologic anomalies likely contribute to the severe subfertility of PCSK4-deficient male mice.

acrosome reaction, fertilization, sperm, sperm capacitation, sperm maturation

¹ Supported by a grant from the Natural Sciences and Engineering Research Council of Canada.

² Correspondence: M. Mbikay Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9. FAX: 613 761 4355; mmbikay{at}ohri.ca

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