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

doi:10.1073/pnas.051630698

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

^*Friedrich Miescher Institute, Maulbeerstrasse 66, CH 4058 Basel, Switzerland; and ^†Sterility and Gynecology Endocrinology Clinic, Department of Gynecology and Obstetrics, Geneva University Hospital, CH 1211 Geneva, Switzerland

Communicated by Eric M. Shooter, Stanford University School of Medicine, Stanford, CA (received for review December 12, 2000)

Abstract

Understanding infertility and sterility requires knowledge of the molecular mechanisms underlying sexual reproduction. We have found that male mice deficient 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 to inadequate semen coagulation and deficient vaginal plug formation upon copulation. Progressive morphological changes of the seminal vesicles also are observed. Consistent with these findings, abnormal PN-1 expression was found in the semen of men displaying seminal dysfunction. The data demonstrate that the level of extracellular proteolytic activity is a critical element in controlling male fertility.