Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1

Understanding infertility and sterility requires knowledge of the molecular mechanisms underlying sexual reproduction. We have found that male mice de ficient for the gene encoding the protease inhibitor protease nexin-1 (PN-1 ) show a marked impairment in fertility from the onset of sexual maturity. Absence of PN-1 results in altered semen protein composition, which leads t o inadequate semen coagulation and deficient vaginal plug formation upon co pulation. Progressive morphological changes of the seminal vesicles also ar e observed. Consistent with these findings, abnormal PN-1 expression was fo und in the semen of men displaying seminal dysfunction. The data demonstrat e that the level of extracellular proteolytic activity is a critical elemen t in controlling male fertility.