This project focuses on the structure and function of the oligosaccharide moieties of the mouse zona pellucida (mZP) and how this extracellular glycocalyx that surrounds the egg interacts with complementary molecules on the surface of spermatozoa. Previous evidence strongly suggests that the sperm binding activity of mZP is associated with its oligosaccharide portion. Recent studies in the applicant's laboratory have demonstrated for the first time the presence of N-linked polylactosaminyl glycans and an O-linked trisaccharide that are thought to have important roles in sperm-egg recognition and binding. To assess the bioactivity of these oligosaccharides, the proposal has five specific aims: (1) to purify mZP2 and mZP3, and then cleave and radiolabel the N-linked glycans and O-linked trisaccharide, (2) to assess the functional role of the radiolabeled N-linked and O-linked glycans in sperm-egg recognition and binding, (3) to isolate and chemically characterize functional N-linked glycan(s), (4) to synthesize the O-linked trisaccharide, examine its function, and the mechanism underlying the formation of the sperm surface antigen-trisaccharide complex, and (5) to identify and chemically characterize the mouse sperm plasma membrane (PM) proteins recognized by the N-linked and/or O-linked glycans. When completed, this study will be the first published report on structure-function diversity of both N-linked and O-linked oligosaccharides. After the complementary molecules (i.e., the bioactive glycans on ZP glycoproteins and complementary receptors on sperm PM) are identified in the selected strain of experimental mice, it will be possible to address the question of interspecies and intraspecies relationships during interactions of opposite gametes. Collectively, these studies will further our understanding of the mechanism of sperm-egg interaction and fertilization in the mouse, and they will provide needed information for the regulation of the fertilization processes in other species, including humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD034041-02
Application #
2673966
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1997-08-01
Project End
2002-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Tulsiani, D R; Abou-Haila, A (2015) Biology of male fertility control: an overview of various male contraceptive approaches. Minerva Ginecol 67:169-83
Abou-Haila, A; Bendahmane, M; Tulsiani, D R (2014) Significance of egg's zona pellucida glycoproteins in sperm-egg interaction and fertilization. Minerva Ginecol 66:409-19
Tulsiani, Daulat R P; Abou-Haila, Aida (2014) Importance of male fertility control in family planning. Endocr Metab Immune Disord Drug Targets 14:134-44
Abou-haila, Aida; Tulsiani, Daulat R P (2009) Signal transduction pathways that regulate sperm capacitation and the acrosome reaction. Arch Biochem Biophys 485:72-81
Tulsiani, Daulat R P; Zeng, Hai-Tao; Abou-Haila, Aida (2007) Biology of sperm capacitation: evidence for multiple signalling pathways. Soc Reprod Fertil Suppl 63:257-72
Tulsiani, Daulat R P; Abou-Haila, Aida (2004) Is sperm capacitation analogous to early phases of Ca2+-triggered membrane fusion in somatic cells and viruses? Bioessays 26:281-90
Zeng, Hai-Tao; Tulsiani, Daulat R P (2003) Calmodulin antagonists differentially affect capacitation-associated protein tyrosine phosphorylation of mouse sperm components. J Cell Sci 116:1981-9
Abou-Haila, Aida; Tulsiani, Daulat R P (2003) Evidence for the capacitation-associated membrane priming of mouse spermatozoa. Histochem Cell Biol 119:179-87
Tulsiani, Daulat R P (2003) Glycan modifying enzymes in luminal fluid of rat epididymis: are they involved in altering sperm surface glycoproteins during maturation? Microsc Res Tech 61:18-27
Bendahmane, Malika; Tulsiani, Daulat R P (2003) Capacitated acrosome-intact mouse spermatozoa bind to Sepharose beads coated with functional neoglycoproteins. Arch Biochem Biophys 415:203-12

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