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2. Endometrial Proteins

Author

Koistinen, R., Julkunen, M., Riittinen, L., Suikkari, A. M., Seppälä, M., Chapman, Michael G., editor, Grudzinskas, J. Gedis, editor, and Chard, Tim, editor

Published
1991
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9. Glycosylation failure extends to glycoproteins in gestational diabetes mellitus: Evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-A

Author

Lee, CL, Seppälä, M, Morris, HR, Panico, M, Tissot, B, Lee, KF, Chu, IK, Pang, PC, Koistinen, R, Chiu, PCN, Dell, A, Yeung, WSB, and Koistinen, H

Subjects
Diabetes, Gestational - metabolism, Pregnancy Proteins - metabolism, Amniotic Fluid - metabolism, Glycoproteins - metabolism, N-Acetylneuraminic Acid - metabolism
Abstract

OBJECTIVE - Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy. Patients with GDM are at risk for high fetal mortality and gestational complications associated with reduced immune tolerance and abnormal carbohydrate metabolism. Glycodelin-A (GdA) is an abundant decidual glycoprotein with glycosylation-dependent immunomodulatory activities. We hypothesized that aberrant carbohydrate metabolism in GDM was associated with changes in glycosylation of GdA, leading to defective immunomodulatory activities. RESEARCH DESIGN AND METHODS - GdA in the amniotic fluid from women with normal (NGdA) and GDM (DGdA) pregnancies was purified by affinity chromatography. Structural analysis of protein glycosylation was preformed by lectin-binding assay and mass spectrometry. Cytotoxicity, cell death, cytokine secretion, and GdA binding of the GdA-treated lymphocytes and natural killer (NK) cells were determined. The sialidase activity in the placental tissue from normal and GDM patients was measured. RESULTS - GDM affected the glycosylation but not the protein core of GdA. Specifically, DGdA had a lower abundance of α2-6-sialylated and high-mannose glycans and a higher abundance of glycans with Sda (NeuAcα2-3[GalNAcβ1-4]Gal) epitopes compared with NGdA. DGdA had reduced immuosuppressive activities in terms of cytotoxicity on lymphocytes, inhibitory activities on interleukin (IL)-2 secretion by lymphocytes, stimulatory activities on IL-6 secretion by NK cells, and binding to these cells. Desialylation abolished the immunomodulation and binding of NGdA. Placental sialidase activity was increased in GDM patients, which may account for the reduced sialic acid content of DGdA. CONCLUSIONS - Taken together, this study provides the first direct evidence for altered enzymatic glycosylation and impaired bioactivity of GdA in GDM patients. © 2011 by the American Diabetes Association., published_or_final_version

Published
2011

11. Double-blind placebo controlled study: Human biosynthetic growth hormone for assisted reproductive technology.

Author

Koistinen R., Healy D.L., Seppala M., Suikkari A.-M., MacLachlan V., Koistinen R., Healy D.L., Seppala M., Suikkari A.-M., and MacLachlan V.

Abstract

Objective: To study whether the effect of cotreatment with human biosynthetic GH improves the outcome of poor IVF responders. Design(s): A double-blind placebo-controlled study using a GnRH agonist (GnRH-a) and gonadotropin in a 'boost' flare-up protocol for ovarian stimulation together with either placebo, 4, or 12 IU of human GH followed by oocyte retrieval and IVF-ET. Patient(s): Twenty-two patients with previously demonstrated poor responses in at least two assisted reproductive technology cycles were recruited. Intervention(s): Pretreatment and post-treatment blood samples and daily morning blood samples during ovarian stimulation were collected after an overnight fast. Human GH or placebo and GnRH-a were administered SC; gonadotropin was administered IM. Oocytes were collected by ultrasound- guided transvaginal aspiration of follicles. Embryos were cultured in vitro and transferred transcervically. Main Outcome Measure(s): Serum E2, FSH, GH, insulin-like growth factor-1 (IGF-I), IGF binding protein 1 (IGFBP-1), and IGFBP-3 concentrations. Number of FSH ampules, follicles, oocytes, embryos, and pregnancies. Result(s): No improvement in cycle outcome was demonstrated with daily adjuvant human GH administration with either 4 or 12 IU. Serum IGF-I levels were highest in the 12 IU human GH group and lowest in the placebo group. Serum IGFBP-3 levels increased 2 days after IGF-I levels in the 12 IU human GH group only. Serum IGFBP-1 levels were unchanged in all groups. Conclusion(s): Poor IVF responders do not benefit from cotreatment with human GH during their ovarian stimulation.

Published
2012

12. Glycodelin and beta-lactoglobulin, lipocalins with a high structural similarity, differ in ligand binding properties

Author

Koistinen, H., Koistinen, R., Burova, T.V., Choiset, Yvan, Haertlé, Thomas, Laboratoire d'étude des interactions des molécules alimentaires, Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
LIPOCALINE, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
1999

14. Glycodelin-A as a modulator of trophoblast invasion

Author

Lam, K. K.W., primary, Chiu, P. C.N., additional, Chung, M.-K., additional, Lee, C.-L., additional, Lee, K.-F., additional, Koistinen, R., additional, Koistinen, H., additional, Seppala, M., additional, Ho, P.-C., additional, and Yeung, W. S.B., additional

Published
2009
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45. Glycosylation failure extends to glycoproteins in gestational diabetes mellitus: evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-A.

Author

Lee CL, Chiu PC, Pang PC, Chu IK, Lee KF, Koistinen R, Koistinen H, Seppälä M, Morris HR, Tissot B, Panico M, Dell A, Yeung WS, Lee, Cheuk-Lun, Chiu, Philip C N, Pang, Poh-Choo, Chu, Ivan K, Lee, Kai-Fai, Koistinen, Riitta, and Koistinen, Hannu

Abstract

Objective: Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy. Patients with GDM are at risk for high fetal mortality and gestational complications associated with reduced immune tolerance and abnormal carbohydrate metabolism. Glycodelin-A (GdA) is an abundant decidual glycoprotein with glycosylation-dependent immunomodulatory activities. We hypothesized that aberrant carbohydrate metabolism in GDM was associated with changes in glycosylation of GdA, leading to defective immunomodulatory activities.Research Design and Methods: GdA in the amniotic fluid from women with normal (NGdA) and GDM (DGdA) pregnancies was purified by affinity chromatography. Structural analysis of protein glycosylation was preformed by lectin-binding assay and mass spectrometry. Cytotoxicity, cell death, cytokine secretion, and GdA binding of the GdA-treated lymphocytes and natural killer (NK) cells were determined. The sialidase activity in the placental tissue from normal and GDM patients was measured.Results: GDM affected the glycosylation but not the protein core of GdA. Specifically, DGdA had a lower abundance of α2-6-sialylated and high-mannose glycans and a higher abundance of glycans with Sda (NeuAcα2-3[GalNAcβ1-4]Gal) epitopes compared with NGdA. DGdA had reduced immuosuppressive activities in terms of cytotoxicity on lymphocytes, inhibitory activities on interleukin (IL)-2 secretion by lymphocytes, stimulatory activities on IL-6 secretion by NK cells, and binding to these cells. Desialylation abolished the immunomodulation and binding of NGdA. Placental sialidase activity was increased in GDM patients, which may account for the reduced sialic acid content of DGdA.Conclusions: Taken together, this study provides the first direct evidence for altered enzymatic glycosylation and impaired bioactivity of GdA in GDM patients. [ABSTRACT FROM AUTHOR]

Published
2011
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47. Inflammatory markers and retinopathy in pregnancies complicated with Type I diabetes.

Author

Loukovaara, S., Immonen, I., Koistinen, R., Hiilesmaa, V., and Kaaja, R.

Subjects
BIOMARKERS, INFLAMMATION, PREGNANCY, PEPTIDES, DIABETES, INTERLEUKIN-6, ENZYME-linked immunosorbent assay
Abstract

AIM:The relation of maternal cytokine levels to retinopathy progression during diabetic pregnancy is a less studied subject. Therefore, we investigated levels of systemic proinflammatory markers, C-reactive peptide (CRP), interleukin-6 (IL-6) and circulating vascular cell adhesion molecule-1 (VCAM-1) during pregnancy and postpartum in relation to the progression of diabetic retinopathy (DR). METHODS:A prospective follow-up study of 39 pregnant women with Type I diabetes and eight nondiabetic pregnant women was performed. DR was graded from fundus photographs. Plasma levels of systemic proinflammatory markers were measured by immunofluorometric assay (CRP) and by enzyme-linked immunosorbent assay (IL-6 and VCAM-1) in the first, second (diabetics only), third trimester of pregnancy, and 3 and 6 months postpartum (diabetics only). RESULTS: Our diabetic women had good glycaemic control (HbA1c 6.9±0.8). The levels of IL-6, VCAM-1, and CRP did not differ between diabetic and nondiabetic women throughout pregnancy and postpartum (repeated measures ANOVA between the groups). An association between CRP and progression of retinopathy was observed in diabetic women (P=0.037). Additional evidence of inter-relationship could be revealed as CRP was higher in those diabetic women with worse glycaemic control (HbA1c) (P=0.038). CONCLUSIONS:During pregnancy and postpartum, levels of proinflammatory factors (IL-6, CRP, VCAM-1) seem to be generally similar in Type I diabetic women compared to nondiabetic controls. However, CRP levels were higher in those diabetic women with progression of retinopathy and in those with worse glycaemic control.Eye (2005) 19, 422-430. doi:10.1038/sj.eye.6701499 Published online 30 July 2004 [ABSTRACT FROM AUTHOR]

Published
2005
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