The goal of the current application is to explore the potential function of a novel mouse seminal vesicle secretory protein in the early events of fertilization, using the mouse as a model. Mammalian sperm requires gaining of capability in the female reproductive tract to fertilize an egg. This process is referred to as """"""""capacitation"""""""". It is believed that many changes occur during capacitation in the capacitating sperm, however, the molecular mechanism is poorly understood more than 40 years after the """"""""capacitation"""""""" concept was first introduced. Both intracellular and extracellular components are suggested to be involved in the capacitation of sperm. Seminal vesicle proteins have been suggested to have certain functions either assisting or preventing sperm capacitation. The applicant has recently identified and purified a novel mouse seminal vesicle secretory protein. This protein was identified by its ability to bind a prostate-made serine protease, prostasin. She tentatively named this seminal vesicle protein as """"""""prostasin-binding protein."""""""" The long-term objective of this project is to investigate the function of serine proteases and serine protease inhibitors (serpin) in mammalian fertilization. The hypothesis being evaluated in the current application is that a seminal vesicle secreted serine protease inhibitor in mouse (mPBP) capable of binding to sperm may have an impact on sperm modification, in turn, affecting the early events of fertilization.
The specific aims for the current application are: (1) to examine the effects of the prostasin-binding protein on sperm capacitation and/or acrosomal reaction, as well as sperm motility, (2) to establish the genetic identity of this new protein by cloning the cDNA from mouse. The results will provide valuable information to the understanding of the biochemical mechanisms of this new protein's potential role in mammalian fertilization. Understanding the mechanisms regulating the early events of fertilization is essential for the development of methods and reagents to manipulate fertilization.
|Chen, Mengqian; Fu, Ya-Yuan; Lin, Chen-Yong et al. (2007) Prostasin induces protease-dependent and independent molecular changes in the human prostate carcinoma cell line PC-3. Biochim Biophys Acta 1773:1133-40|
|Zhang, Heng; Lin, Hai-Yan; Yang, Qing et al. (2007) Expression of prostasin serine protease and protease nexin-1 (PN-1) in rhesus monkey ovary during menstrual cycle and early pregnancy. J Histochem Cytochem 55:1237-44|
|Netzel-Arnett, Sarah; Currie, Brooke M; Szabo, Roman et al. (2006) Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation. J Biol Chem 281:32941-5|
|Chen, Mengqian; Chen, Li-Mei; Chai, Karl X (2006) Androgen regulation of prostasin gene expression is mediated by sterol-regulatory element-binding proteins and SLUG. Prostate 66:911-20|
|Lin, Hai-Yan; Zhang, Heng; Yang, Qing et al. (2006) Expression of prostasin and protease nexin-1 in rhesus monkey (Macaca mulatta) endometrium and placenta during early pregnancy. J Histochem Cytochem 54:1139-47|
|Chen, Mengqian; Chen, Li-Mei; Chai, Karl X (2006) Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of human prostasin gene expression. Biochem Biophys Res Commun 346:1245-53|
|Chen, Li-Mei; Wang, Cindy; Chen, Mengqian et al. (2006) Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation. Am J Physiol Renal Physiol 291:F567-77|
|Chen, Li-Mei; Zhang, Xiaochun; Chai, Karl X (2004) Regulation of prostasin expression and function in the prostate. Prostate 59:1-12|