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 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.
Murer
V
V
Friedrich Miescher Institute, Maulbeerstrasse 66, CH 4058 Basel, Switzerland.
Spetz
J F
JF
Hengst
U
U
Altrogge
L M
LM
de Agostini
A
A
Monard
D
D
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D015849:Plasminogen Inactivators / Q000502:physiology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D012661:Semen / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000378:metabolism; D012669:Seminal Vesicles / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000502:physiology*; D058258:Serpin E2; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology; D014621:Vagina / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D015849:Plasminogen Inactivators; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D029589:Seminal Plasma Proteins; D015842:Serine Proteinase Inhibitors; D058258:Serpin E2