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Misuzu Yamashita^1,, Arata Honda^2,, Atsuo Ogura^1,2, Shin-ichi Kashiwabara¹, Kiyoko Fukami³ and Tadashi Baba^1,*

¹ Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan
² RIKEN, Bioresource Center, Tsukuba Science City, Ibaraki 305-0074, Japan
³ Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Science, Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan

Although the acrosome reaction and subsequent penetration of sperm through the egg zona pellucida (ZP) are essential for mammalian fertilization, the molecular mechanism is still controversial. We have previously identified serine protease Tesp5 identical to Prss21 on the mouse sperm surface as a candidate enzyme involved in sperm penetration through the ZP. Here we show that despite normal fertility of male mice lacking Prss21/Tesp5, the epididymal sperm penetrates the ZP only at a very low rate in vitro, presumably owing to the reduced ability to bind the ZP and undergo the ZP-induced acrosome reaction. The ability of Prss21-null sperm to fuse with the egg in vitro was also impaired severely. Intriguingly, the reduced fertility of Prss21-null epididymal sperm was rescued by exposure of the sperm to the uterine microenvironment and by in vitro treatment of the sperm with uterine fluids. These data suggest the physiological importance of sperm transport through the uterus.

These authors contributed equally to this work.

^* Correspondence: acroman{at}sakura.cc.tsukuba.ac.jp