SERPINE2, a Serine Protease Inhibitor Extensively Expressed in Adult Male Mouse Reproductive Tissues, May Serve as a Murine Sperm Decapacitation Factor1

Abstract

SERPINE2, one of the potent serine protease inhibitors that modulates the activity of plasminogen activator and thrombin, is implicated in many biological processes. In the present study, we purified SERPINE2 from mouse seminal vesicle secretion (SVS), using liquid chromatography and identified it by liquid chromatography/tandem mass spectrometry, and it showed potent inhibitory activity against the urokinase-type plasminogen activator. SERPINE2 was expressed predominantly in seminal vesicles among murine male reproductive tissues. It was immunolocalized to the SVS and mucosal epithelium of the seminal vesicle, epididymis, coagulating gland, and vas deferens. In the testes, SERPINE2 was immunostained in spermatogonia, spermatocytes, spermatids, Leydig cells, and spermatozoa. SERPINE2 was also detected on the acrosomal cap of testicular and epididymal sperm and was suggested to be an intrinsic sperm surface protein. The purified SERPINE2 protein could bind to epididymal sperm. A prominent amount of SERPINE2 was detected on ejaculated and oviductal spermatozoa. Nevertheless, SERPINE2 was detected predominantly on uncapacitated sperm, indicating that SERPINE2 is lost before initiation of the capacitation process. Moreover, SERPINE2 could inhibit in vitro bovine serum albumin-induced sperm capacitation and prevent sperm binding to the egg, thus blocking fertilization. It acts through preventing cholesterol efflux, one of the initiation events of capacitation, from the sperm. These findings suggest that the SERPINE2 protein may play a role as a sperm decapacitation factor.

Single Nucleotide Polymorphisms in Candidate Genes Associated with Fertilizing Ability of Sperm and Subsequent Embryonic Development in Cattle1

“…For example, AVP is antiapoptotic [29,30], and EPAS1 encodes for a transcription factor induced by hypoxia [31]. Furthermore, SERPINE2 can prevent capacitation [32] and may act to prevent premature capacitation. Another gene associated with CR, NT5E, encodes for an enzyme that converts adenosine monophosphate to adenosine [33], which could conceivably affect energy availability or signal transduction.…”

SPINK3 modulates mouse sperm physiology through the reduction of nitric oxide level independently of its trypsin inhibitory activity

“…SERPINE2 inhibits both plasminogen activator and thrombin, and also inhibits in vitro BSA-induced tyrosine phosphorylation of sperm under capacitating conditions by unknown mechanisms (Lu et al 2011). EPPIN, characterized by both WAP-type and Kunitz-type consensus sequences (Wang et al 2005, O'Rand et al 2007, acts a decapacitating factor by modulating the activity of PSA in semenogelin, which inhibits human sperm capacitation (de Lamirande et al 2001).…”

Seminal vesicle protein SVS2 is required for sperm survival in the uterus

“…Notably, the induced ability of fertilization-competent (i.e., capacitated) rabbit sperm is reverted to an incompetent state when it is mixed with seminal plasma; this phenomenon, discovered by Chang and Bedford (2,3), is referred to as "decapacitation." Subsequent to their findings, many studies have focused on identifying the decapacitation factor in the seminal plasma using in vitro assays (4)(5)(6); the seminal plasma is believed to stabilize sperm plasma membranes and prevent uterine sperm from undergoing premature capacitation and acrosomal reaction, an exocytotic process that occurs immediately before sperm-egg fusion (7,8).…”