Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability.
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.
Gyamera-Acheampong
Charles
C
Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.
Tantibhedhyangkul
Julierut
J
Weerachatyanukul
Wattana
W
Tadros
Haidy
H
Xu
Hongbin
H
van de Loo
Jan-W
JW
Pelletier
R-Marc
RM
Tanphaichitr
Nongnuj
N
Mbikay
Majambu
M
D020101:Acrosome Reaction / Q000502:physiology; D000818:Animals; D005260:Female; D005306:Fertilization / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D043484:Proprotein Convertases; D011817:Rabbits; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000201:enzymology*; D013381:Subtilisins; D013737:Testis / Q000378:metabolism; D013997:Time Factors
C489717:Pcsk4 protein, mouse; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins