Testase 1 (ADAM 24) a sperm surface metalloprotease is required for normal fertility in mice

ADAM family members play important roles in various physiological and pathological processes, for example, fertilization, embryogenesis, neurogenesis, and development of asthma and arthritis (Primakoff and Myles, 2000. Trends Genet 16: 83-87; Edwards et al., 2008. Mol Aspects Med 29: 258-289). We previously reported that testase 1 (ADAM 24) is the first identified metalloprotease present on the surface of mature sperm. To investigate a potential role of testase 1 in fertilization, we generated testase 1 deficient mice. Testase 1 null male mice showed reduced fertility, producing only half the number of offspring when compared to wild-type littermates. In a standard in vitro fertilization assay, we found that sperm lacking testase 1 gave rise to polyspermic fertilization, a phenotypic feature that might contribute to failure of normal embryo development due to polyaneuploidy. Furthermore, in vivo, we found that testase 1 null males produced a higher number of polyspermic embryos at the pronuclear stage. These findings suggest that testase 1 is a sperm plasma membrane component which contributes to the prevention of polyspermy at the level of the oocyte plasma membrane.