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J Biol Chem, Vol. 273, Issue 20, 12068-12076, May 15, 1998

Developmental Changes in the Glycosylation of Glycoprotein Hormone Free  Subunit during Pregnancy

Martin Nemansky, N. Rao Thotakura, Curtis D. Lyons, Song Ye, Bruce B. Reinhold, Vernon N. Reinhold, and Diana L. Blithe

From the  Unit of Glycobiology, Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892 and the  Department of Microbiology and Immunology/Mass Spectrometry Resource, Boston University Medical Center, Boston, Massachusetts 02118

Glycoprotein hormone  subunit, in its free form (free ), is a major placental product. Its glycosylation was found to change dramatically during the advancement of pregnancy. In this study, we have analyzed these glycosylation changes in five normal pregnancies. Binding to Lens culinaris lectin increased dramatically in all subjects between weeks 14 and 17 from the last menstrual period, indicating more core fucosylation as well as possible changes in branching of glycans. Studies using Datura stramonium agglutinin confirmed that the type of triantennary branching changed in this period of pregnancy. The precise structural nature of these changes was determined by high-pH anion-exchange chromatography and electrospray ionization mass spectrometry. Amounts of core fucosylation and of triantennary glycans increased substantially from early to late second trimester, and a shift was observed from 14/13- toward predominantly 16/16-branched triantennary structures. The glycosylation changes occurred in all five individuals at the same time period in gestation, suggesting developmental regulation of N-acetylglucosaminyltransferases IV and V and 6-fucosyltransferase during normal pregnancy. These enzymatic activities also appear to be affected in malignant transformation of the trophoblast. Our findings have important implications for the proposed use of specific forms of glycosylation as markers for cancer, as the relative amounts of these glycans in normal pregnancy will be determined by gestational age.

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