The focus of this Center is the gamete as a contraceptive target. Remarkable advances have occurred recently in genomics and proteomics, cell biology, fertilization research and drug discovery. These advances have combined to open new possibilities for contraceptive intervention, directed against gametes, that may have been previously imagined but were unattainable. Most of our projects target sperm, though one project proposes a potential egg target. Anti-sperm contraception can block sperm function or sperm development. Our Center's projects include both targets. A major theme of the Center is small molecule inhibitors to block sperm function. Our Center is actively studying sperm plasma membrane proteins that function in sperm-egg interaction and we propose screens for small molecules that inhibit these sperm proteins and thus prevent fertilization. A second theme is to block sperm development. Novel pharmacological strategies to derail the complex process of sperm production are proposed here. All of us who study sperm development are aware of important advances in spermatogenesis and realize that new, feasible contraceptive targets are being identified. Thus, we have proposed an expansion of our target list in spermatogenesis, increasing our scope and chances of developing new products for birth control.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD029125-16
Application #
7020004
Study Section
Special Emphasis Panel (ZHD1-DRG-D (11))
Program Officer
Blithe, Diana
Project Start
1997-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2008-02-29
Support Year
16
Fiscal Year
2006
Total Cost
$1,227,632
Indirect Cost
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Sutton, Keith A; Jungnickel, Melissa K; Ward, Christopher J et al. (2006) Functional characterization of PKDREJ, a male germ cell-restricted polycystin. J Cell Physiol 209:493-500
Yu, Junying; Deng, Manqi; Medvedev, Sergey et al. (2004) Transgenic RNAi-mediated reduction of MSY2 in mouse oocytes results in reduced fertility. Dev Biol 268:195-206
Yu, Junying; Hecht, Norman B; Schultz, Richard M (2003) Requirement for RNA-binding activity of MSY2 for cytoplasmic localization and retention in mouse oocytes. Dev Biol 255:249-62
Talbot, Prudence; Shur, Barry D; Myles, Diana G (2003) Cell adhesion and fertilization: steps in oocyte transport, sperm-zona pellucida interactions, and sperm-egg fusion. Biol Reprod 68:1-9
Miller, Christopher J; Lu, Fabien X (2003) Anti-HIV and -SIV immunity in the vagina. Int Rev Immunol 22:65-76
Tollner, Theodore L; Yudin, Ashley I; Cherr, Gary N et al. (2003) Real-time observations of individual macaque sperm undergoing tight binding and the acrosome reaction on the zona pellucida. Biol Reprod 68:664-72
Yu, Junying; Hecht, Norman B; Schultz, Richard M (2002) RNA-binding properties and translation repression in vitro by germ cell-specific MSY2 protein. Biol Reprod 67:1093-8
Tollner, Theodore L; Overstreet, James W; Li, Ming W et al. (2002) Lignosulfonic acid blocks in vitro fertilization of macaque oocytes when sperm are treated either before or after capacitation. J Androl 23:889-98
Tollner, T L; Overstreet, J W; Branciforte, D et al. (2002) Immunization of female cynomolgus macaques with a synthetic epitope of sperm-specific lactate dehydrogenase results in high antibody titers but does not reduce fertility. Mol Reprod Dev 62:257-64
Deng, X; Meyers, S A; Tollner, T L et al. (2002) Immunological response of female macaques to the PH-20 sperm protein following injection of recombinant proteins or synthesized peptides. J Reprod Immunol 54:93-115

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