In mammals, sperm migrate through the female reproductive tract to reach the egg. We previously reported that seminal vesicle secretion 2 (SVS2), which is a 40-kDa basic protein and a major component of the copulatory plug, enters the uterine with ejaculated sperm and acts as a decapacitation factor in in vitro fertilization (Kawano and Yoshida, 2007; Kawano et al., 2008); however, our understanding of the sperm journey is highly limited. To study the role of SVS2 in vivo, we here focused on defining a function of SVS2 in female reproductive tract.

Male mice lacking SVS2 displayed prominently reduced fertility, but their epididymal sperm were able to fertilize eggs normally in vitro, raising the possibility that SVS2 is essential for in vivo fertilization. At the copulation, formation of a copulatory plug in female vagina did not occur, resulting in a strongly reduced number of uterine sperm. Surprisingly, even when artificial insemination (AI) was performed with silicon as a substitute for the plug, sperm fertility without SVS2 remained severely reduced because the sperm were already dead in the uterus. When the sperm were used for AI without SVS2, the cell and nuclear membranes were fractured not only in the acrosome but in all regions of the sperm. The rate of membrane-disrupted sperm was significantly higher without SVS2 (PI, 72.9 ± 3.4%; eosin, 93.9 ± 2.3%), than with SVS2 (PI, 12.8 ± 3.1%; eosin, 14.0 ± 4.7%). From these results, we concluded that SVS2 acts to protect sperm against the uterine spermicide(s) by coating the sperm surface.

Our finding opens the possibility that a competitive balance between death and survival in the uterus contributes to sperm selection. Based on this system, mammalian males may develop a protective strategy against female attack at the gamete level.