These studies will identify and characterize key components of the intrinsic genetic program that controls development and function of male germ cells. The approaches currently being applied are to identify genes expressed specifically in male germ cells, use the gene knockout approach to define the roles of the proteins they encode, employ yeast two-hybrid assays and deletion mutagenesis to identify protein-protein interactions essential for development of the male gamete, and prepare antisera to determine the temporal-spatial distribution of specific gene products. Many genes are expressed only in male germ cells and selected genes are being studied that encode proteins whose functions are essential for four novel aspects of gamete development and/or function. (1) GAPDS and PGK2 are enzymes in the glycolytic pathway produced by spermatogenic cell-specific genes that are orthologues of those expressed in all other tissues. These enzymes bind to the fibrous sheath, a cytoskeletal structure in the sperm flagellum. (2) AKAP4, AKAP3, and CABYR contain protein kinase A (PKA) protein anchoring sites and also are components of the fibrous sheath. (3) Protamines 1 and 2 are highly basic nuclear proteins that replace histones following meiosis. Sperm lack nucleosomes and the protamines are essential for the high degree of DNA compaction in their haploid nuclei. (4) Cdc20 associates with the cyclosome/anaphase-promoting complex (APC) and is essential for APC-dependent proteolysis of cell cycle proteins in the metaphase to anaphase transition. We have identified speriolin, a novel Cdc20-binding factor in spermatogenic cells that might regulate the function of Cdc20 during meiosis in the spermatogenic cells. The first three groups of genes are expressed exclusively during the post-meiotic phase of spermatogenesis, while the last gene is expressed just prior to this phase. Future studies will determine how paracrine, signal transduction, and genetic pathways contribute to the coordinate expression of these genes in spermatogenic cells.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Chen, Liang-Yu; Brown, Paula R; Willis, William B et al. (2014) Peritubular myoid cells participate in male mouse spermatogonial stem cell maintenance. Endocrinology 155:4964-74
Chaffee, Blake R; Shang, Fu; Chang, Min-Lee et al. (2014) Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly. Development 141:3388-98
Brown, Paula R; Odet, Fanny; Bortner, Carl D et al. (2014) Reporter mice express green fluorescent protein at initiation of meiosis in spermatocytes. Genesis 52:976-84
Nakamura, Noriko; Dai, Qunsheng; Williams, Jason et al. (2013) Disruption of a spermatogenic cell-specific mouse enolase 4 (eno4) gene causes sperm structural defects and male infertility. Biol Reprod 88:90
Eddy, Edward M; Chen, Liang-Yu (2013) Location, location, location: how does a spermatogonium know it is a spermatogonial stem cell (SSC)? Biol Reprod 88:132
Odet, Fanny; Gabel, Scott; London, Robert E et al. (2013) Glycolysis and mitochondrial respiration in mouse LDHC-null sperm. Biol Reprod 88:95
Xie, Fang; Eddy, Edward M; Conti, Marco (2013) Analysis of signaling pathways controlling flagellar movements in mammalian spermatozoa. Methods Enzymol 524:91-104
Arao, Yukitomo; Hamilton, Katherine J; Goulding, Eugenia H et al. (2012) Transactivating function (AF) 2-mediated AF-1 activity of estrogen receptor ? is crucial to maintain male reproductive tract function. Proc Natl Acad Sci U S A 109:21140-5
Davis, Vicki L; Newbold, Retha R; Couse, John F et al. (2012) Expression of a dominant negative estrogen receptor alpha variant in transgenic mice accelerates uterine cancer induced by the potent estrogen diethylstilbestrol. Reprod Toxicol 34:512-21
Geyer, Christopher B; Saba, Rie; Kato, Yuzuru et al. (2012) Rhox13 is translated in premeiotic germ cells in male and female mice and is regulated by NANOS2 in the male. Biol Reprod 86:127

Showing the most recent 10 out of 22 publications