Insights into the hyperglycosylation of human chorionic gonadotropin revealed by glycomics analysis

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is essential for the maintenance of pregnancy. Glycosylation of hCG is known to be essential for its biological activity. "Hyperglycosylated" variants secreted during early pregnancy have been proposed to be involved in init...

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Published in:PloS one Vol. 15; no. 2; p. e0228507
Main Authors: Ibeto, Linda, Antonopoulos, Aristotelis, Grassi, Paola, Pang, Poh-Choo, Panico, Maria, Bobdiwala, Shabnam, Al-Memar, Maya, Davis, Paul, Davis, Mark, Norman Taylor, Julian, Almeida, Paula, Johnson, Mark R., Harvey, Richard, Bourne, Tom, Seckl, Michael, Clark, Gary, Haslam, Stuart M., Dell, Anne
Format: Journal Article
Language:English
Published: United States Public Library of Science 11.02.2020
Public Library of Science (PLoS)
Subjects:
Antigenic determinants
Antigens
Biological activity
Biology and Life Sciences
Biomarkers
Cancer
Carbohydrate Sequence
Chorionic gonadotropin
Chorionic Gonadotropin, beta Subunit, Human - blood
Chorionic Gonadotropin, beta Subunit, Human - metabolism
Chorionic Gonadotropin, beta Subunit, Human - urine
Chorionic gonadotropins
Comparative analysis
Cytotoxicity
Diagnostic systems
Diseases
Embryo
Embryos
Epitopes
Female
Female identity
Gestation
Gestational Age
Gestational Trophoblastic Disease - blood
Gestational Trophoblastic Disease - metabolism
Gestational Trophoblastic Disease - urine
Glycan
Glycomics - methods
Glycoproteins
Glycosylation
Gonadotropins
Gynecology
Health aspects
Hormones
Humans
Identity
Implantation
Killer cells
Life sciences
Mass spectrometry
Mass spectroscopy
Medicine and Health Sciences
Miscarriage
N-glycans
Natural killer cells
Novels
Obstetrics
Physical Sciences
Pituitary (anterior)
Pituitary hormones
Placental hormones
Polysaccharides
Polysaccharides - metabolism
Preeclampsia
Pregnancy
Pregnant women
Protein Processing, Post-Translational
Research and Analysis Methods
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectroscopy
Tandem Mass Spectrometry
Time
Toxicity
Trophoblastic disease
Tumors
Urine
Womens health
United Kingdom > UK
United States > US
Missouri
ISSN:1932-6203, 1932-6203
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Summary:Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is essential for the maintenance of pregnancy. Glycosylation of hCG is known to be essential for its biological activity. "Hyperglycosylated" variants secreted during early pregnancy have been proposed to be involved in initial implantation of the embryo and as a potential diagnostic marker for gestational diseases. However, what constitutes "hyperglycosylation" is not yet fully understood. In this study, we perform comparative N-glycomic analysis of hCG expressed in the same individuals during early and late pregnancy to help provide new insights into hCG function, reveal new targets for diagnostics and clarify the identity of hyperglycosylated hCG. hCG was isolated in urine collected from women at 7 weeks and 20 weeks' gestation. hCG was also isolated in urine from women diagnosed with gestational trophoblastic disease (GTD). We used glycomics methodologies including matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry (MS) and MS/MS methods to characterise the N-glycans associated with hCG purified from the individual samples. The structures identified on the early pregnancy (EP-hCG) and late pregnancy (LP-hCG) samples corresponded to mono-, bi-, tri-, and tetra-antennary N-glycans. A novel finding was the presence of substantial amounts of bisected type N-glycans in pregnancy hCG samples, which were present at much lower levels in GTD samples. A second novel observation was the presence of abundant LewisX antigens on the bisected N-glycans. GTD-hCG had fewer glycoforms which constituted a subset of those found in normal pregnancy. When compared to EP-hCG, GTD-hCG samples had decreased signals for tri- and tetra-antennary N-glycans. In terms of terminal epitopes, GTD-hCG had increased signals for sialylated structures, while LewisX antigens were of very minor abundance. hCG carries the same N-glycans throughout pregnancy but in different proportions. The N-glycan repertoire is more diverse than previously reported. Bisected and LewisX structures are potential targets for diagnostics. hCG isolated from pregnancy urine inhibits NK cell cytotoxicity in vitro at nanomolar levels and bisected type glycans have previously been implicated in the suppression of NK cell cytotoxicity, suggesting that hCG-related bisected type N-glycans may directly suppress NK cell cytotoxicity.
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Competing Interests: Affiliation with Mologic LTD UK I can confirm that this commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in guide for authors http://journals.plos.org/plosone/s/competing-interests).
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0228507