Molecular regulation in reproduction

University Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

The Laboratories for Reproductive Biology proposes to continue its Specialized Cooperative Center for Research in Reproduction with focus on molecular mechanisms regulating reproductive processes. Four interrelated subprojects will utilize three core facilities. I. "Endometrial integrins and uterine receptivity". Bruce A. Lessey, M.D., Ph.D., will further delineate the endometrial signaling pathways required for uterine receptivity to embryo implantation and determine the mechanism by which polycystic ovaries with hyperandrogenism causes loss of uterine receptivity. II. "Molecular determinants of androgen receptor function", Elizabeth M. Wilson, Ph.D., will analyze androgen receptor (AR) gene mutations causing androgen insensitivity syndrome (AIS) to test the hypothesis that multiple intra and intermolecular domain specific protein interactions control ligand-AR mediated gene activation. Focus will be on structural determinants of the NH2/carboxyl-terminal interaction, AR degradation signals, p160 coactivation, and AR interaction with other coregulators. Androgen resistant fibroblasts that lack an AR gene mutation will be analyzed to identify a missing co-activator required for AR action. III. "Function of glyceraldehyde 3-phosphate dehydrogenase- S (GAPDS) during spermatogenesis and fertilization", Deborah A. O'Brien , Ph.D., will analyze GAPDS knockout and transgenic mice to identify defects in sperm function and test the hypothesis that anchoring of GAPDS to the fibrous sheath is essential for normal sperm glycolysis, hyperactivated motility and fertilization. Sperm proteins that interact with GAPDS will be identified, and the role of GAPDS in assembly of sperm glycolytic enzymes will be investigated. Key amino acids responsible for the novel enzymatic properties of GAPDS will be established. IV. "Functional characterization of the testis-specific histone binding protein, NASP, during spermatogenesis", Michael G. O'Rand, Ph.D., will test the hypothesis that NASP is important for normal spermatogenic cell function during both mitosis and meiosis. This proposal seeks to establish the role NASP plays in the transport and transfer of specific histones to chromatin during meiosis and mitosis. It will determine how NASP is regulated and whether NASP stores and/or transports transition proteins and protamines to the DNA during spermiogenesis . Each project will be assisted by Cell Separation and Tissue Culture, Immunotechnology-Histochemistry, and Administrative Cores.