Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope
| Autor: | J Schlatterer, Steven Birken, Galina Kovalevskaya, T Kakuma, JF O'Connor, M Cohen, Mark V. Sauer, Steven R. Lindheim, A. C. Kelly, N Ozaki |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
endocrine system
medicine.medical_specialty Glycosylation Endocrinology Diabetes and Metabolism medicine.medical_treatment Population Fertilization in Vitro Chorionic Gonadotropin Human chorionic gonadotropin Epitopes Endocrinology Pregnancy Internal medicine medicine Humans Protein Isoforms education reproductive and urinary physiology Fetus education.field_of_study In vitro fertilisation biology medicine.disease Embryo Transfer Embryo transfer Abortion Spontaneous Pregnancy Trimester First biology.protein Term Birth Electrophoresis Polyacrylamide Gel Female Immunoradiometric Assay Antibody Biomarkers |
| Zdroj: | The Journal of endocrinology. 172(3) |
| ISSN: | 0022-0795 |
| Popis: | Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope. |
| Databáze: | OpenAIRE |
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