Abstract
Glycoprotein hormone alpha subunit, in its free form (free alpha), 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 1-->4/1-->3- toward predominantly 1-->6/1-->6-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 alpha6-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.
Highlights
Glycoprotein hormone ␣ subunit, in its free form, is a major placental product
Lectin Affinity Chromatography—Free ␣ subunit was purified from 24-h urine collections throughout the pregnancies of five healthy individuals
Samples of free ␣ taken throughout the second trimester of each pregnancy were analyzed by lectin affinity chromatography on columns containing LcH-agarose (Fig. 1) or DSA gel (Fig. 2)
Summary
Vol 273, No 20, Issue of May 15, pp. 12068 –12076, 1998 Printed in U.S.A. Developmental Changes in the Glycosylation of Glycoprotein Hormone Free ␣ Subunit during Pregnancy*. The free form of ␣ subunit generally contains more elaborate oligosaccharide branching as well as higher amounts of core fucosylation than ␣ subunit obtained from dissociated hormone [8, 9] These characteristic glycosylation patterns prevent secreted free ␣ subunits from combining with  subunits that might be encountered extracellularly, ensuring a population of free ␣ molecules [9, 10]. Glycosylation patterns of pregnancy-related glycoproteins should change concurrently with the decline of the invasiveness of trophoblast tissue during the early second trimester of normal pregnancy This theory is supported by the different glycosylation patterns found on hCG1 (8, 15, 26 –28) and on free ␣ subunit from normal pregnancy [8, 26], choriocarcinoma [22,23,24], and non-trophoblastic neoplasms [25, 29].
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