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CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the Oglycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man 5 -Man 9 GlcNAc 2 . The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 (derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.

Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by organs of the male reproductive tract. The components of this fluid have been implicated in the suppression of immune response, agonistic effects on sperm-egg binding, and promotion of successful implantation of the human embryo. Fractionation followed by biophysical analyses revealed that free oligosaccharides constitute a major component of the total glycoconjugates within seminal plasma. Significant findings of our analyses include the following: (i) the concentration of free oligosaccharides is 0.3-0.4 mg/ml; (ii) monoand difucosylated forms of the disaccharide lactose are major components; (iii) many of the remaining oligosaccharides are also rich in fucose and carry Lewis x and/or Lewis y epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence (GlcNAc␤1-3/4Glc) not reported in human milk oligosaccharides; (v) oligosaccharides in seminal plasma exclusively express type 2 (Gal␤1-4GlcNAc) but not the type 1 sequences (Gal␤1-3GlcNAc) that predominate in human milk glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is far less than human milk oligosaccharides. The agonistic effect of both fucose and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that fucosylated oligosaccharides may also promote fertilization in the female reproductive tract.Human semen contains a variety of different cell types including sperm, neutrophils, monocytes, and lymphocytes (reviewed in Ref. 1). If incubated for a brief period of time, semen undergoes a process known as liquefaction that leads to clearing of this fluid and a partial loss of its viscosity (2). Centrifugation of partially liquefied semen leads to the separation of the cellular components from the viscous acellular fluid known as human seminal plasma (HSP). 1 HSP is more than simply a liquid medium for transporting sperm into the vagina. It is an extremely complex mixture of proteins, glycoproteins, peptides, glycopeptides, and prostaglandins secreted by the organs of the male reproductive tract (reviewed in Ref. 1). A plethora of different studies indicate that HSP supports sperm function, modulates maternal immune responses directed against sperm, and promotes successful implantation of the human embryo (reviewed in Refs. 1, 3, and 4). The components of HSP may therefore profoundly impact male fertility in the female reproductive tract.Previous studies confirm that HSP contains a specific glycoprotein with immunomodulatory activities (5) now known as glycodelin-S (6). Glycodelin-S also promotes human sperm binding to homologous zona pellucida in the hemizona assay system (6). This intriguing combination of biological activities led us to investigate further the glycosylation of other components associated with HSP. By using fast atom bombardment (FAB) and electrospray (ES) mass spectrometry to screen HSP for novel glycoconjugates (7), we have made the surprising disc...

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