Germ Cell Survival Through Carbohydrate-Mediated Interaction with Sertoli Cells

Spermatogenesis is a precisely regulated process in which the germ cells closely interact with Sertoli cells. The molecular basis of this cell-cell adhesion is unknown. Here, we demonstrate that targeted disruption of Man2a2, a gene encoding α-mannosidase IIx (MX), an enzyme that forms intermediate asparagine-linked carbohydrates (N-glycans), results in Man2a2 null males that are largely infertile. The Man2a2 null spermatogenic cells fail to adhere to Sertoli cells and are prematurely released from the testis to epididymis. We identified anN-glycan structure that plays a key role in germ cell–Sertoli cell adhesion and showed that a specific carbohydrate was required for spermatogenesis.

[1]  J. Dennis,et al.  Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation , 2001, Nature.

[2]  J. Marth,et al.  Genetic remodeling of protein glycosylation in vivo induces autoimmune disease. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Stegelmeier,et al.  Locoweeds: effects on reproduction in livestock. , 1999, Journal of natural toxins.

[4]  S. Tsuboi,et al.  Branched O‐linked oligosaccharides ectopically expressed in transgenic mice reduce primary T‐cell immune responses , 1997, The EMBO journal.

[5]  D. Tulsiani,et al.  Mammalian fertilization: a carbohydrate-mediated event. , 1997, Biology of reproduction.

[6]  J. Marth,et al.  Alpha-Mannosidase-II Deficiency Results in Dyserythropoiesis and Unveils an Alternate Pathway in Oligosaccharide Biosynthesis , 1997, Cell.

[7]  Petr Malý,et al.  The α(1,3)Fucosyltransferase Fuc-TVII Controls Leukocyte Trafficking through an Essential Role in L-, E-, and P-selectin Ligand Biosynthesis , 1996, Cell.

[8]  M. Mattei,et al.  Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Kerr,et al.  Macro, micro, and molecular research on spermatogenesis: The quest to understand its control , 1995, Microscopy research and technique.

[10]  M. Fukuda,et al.  Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells , 1995, The Journal of experimental medicine.

[11]  B. Jégou The Sertoli-germ cell communication network in mammals. , 1993, International review of cytology.

[12]  D. Tulsiani,et al.  Asparagine-linked glycoprotein biosynthesis in rat epididymis. Presence of a mannosidase II-like enzyme. , 1991, The Biochemical journal.

[13]  D. Tulsiani,et al.  Human sperm plasma membranes possess alpha-D-mannosidase activity but no galactosyltransferase activity. , 1990, Biology of reproduction.

[14]  D. Tulsiani,et al.  Novel alpha-D-mannosidase of rat sperm plasma membranes: characterization and potential role in sperm-egg interactions , 1989, The Journal of cell biology.

[15]  R. DePhilip,et al.  Germ cell binding to rat Sertoli cells in vitro. , 1987, Biology of reproduction.

[16]  K. Tung,et al.  Murine Sertoli cells: major histocompatibility antigens and glycoconjugates. , 1983, Journal of reproductive immunology.

[17]  D. Tulsiani,et al.  Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. , 1982, The Journal of biological chemistry.