Glycodelins as regulators of early events of reproduction

Seppälä, Markku; Koistinen, Hannu; Dell, Anne; Morris, Howard R.; Oehninger, Sergio; Clark, Gary F.

doi:10.1046/j.1365-2265.1997.1510943.x

Cited by 31 publications

(24 citation statements)

References 28 publications

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“…Glycodelin, also known as placental protein (PP14), was identified immunochemically in extracts of early human placenta (27,28). A potential role for glycodelin in embryonic implantation has been confirmed as facilitating evasion of the maternal immune response (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Angiogenic role for glycodelin in tumorigenesis

Song

Ramaswamy

Ramachandran

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (

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Section: Discussionmentioning

confidence: 99%

Angiogenic role for glycodelin in tumorigenesis

Song

Ramaswamy

Ramachandran

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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“…Glycodelin-A inhibits sperm-oocyte binding (6). Therefore, absence or low abundance of glycodelin-A in endometrium during the periovulatory fertile window is biologically meaningful (55). Certain progestin-based contraceptives increase endometrial glycodelin-A secretion over the fertile midcycle (68), possibly contributing to the contraceptive effect.…”

Section: Fertilisationmentioning

confidence: 99%

Glycodelin in reproductive endocrinology and hormone-related cancer

Seppälä¹,

Koistinen²,

Koistinen

et al. 2009

European Journal of Endocrinology

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Glycodelin is an endocrine-regulated glycoprotein that has significant effects on immune cells, apoptosis, reproduction, cell adhesion, differentiation and cancer. In reproduction, glycodelin contributes to capacitation and immunoprotection of spermatozoa, and it modulates sperm-oocyte binding, acrosome reaction and implantation. In endocrine-related cancer, the differentiation inducing effects of glycodelin are accompanied by growth restriction of malignant cells, decreased expression of oncogenes, increased expression of tumour suppressor genes and morphological reversion of the malignant phenotype. This review features these properties and clinical connections, highlighting the role of glycosylation in biological actions.

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“…: 91-80-2293-2306; Fax: 91-80-360-0814; E-mail: anjali@biochem.iisc.ernet.in. 1 The abbreviations used are: GdA, glycodelin A; GdS, glycodelin S; PBMC, peripheral blood mononuclear cell; FBS, fetal bovine serum; WT, wild-type; Gd-Bac, baculovirus-expressed glycodelin; mAb, monoclonal antibody; PBS, phosphate-buffered saline.…”

Section: Cells and Cell Lines-peripheral Blood Mononuclear Cells (Pbmcs)mentioning

confidence: 99%

“…1 also known as PP14 (placental protein- 14), is a glycosylated dimeric 162-amino acid protein secreted by human endometrium in the late secretory phase of the menstrual cycle and in the early phase of pregnancy under the regulation of the hormone progesterone (1). Glycodelin is glycosylated at two of the three putative glycosylation sites (Asn 28 and Asn 63 ) (2).…”

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confidence: 99%

Analysis of the Role of Oligosaccharides in the Apoptotic Activity of Glycodelin A

Jayachandran

Shaila

Karande

2004

Journal of Biological Chemistry

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Glycodelin A, also known as placental protein-14, is a multifunctional glycosylated protein secreted by the uterine endometrium during the early phases of pregnancy. It is a known suppressor of T cell proliferation, inducer of T cell apoptosis, and inhibitor of sperm zona binding. Unlike in contraceptive activity, where the glycans on the molecule have been shown to play a crucial role, mutagenesis of the asparagines at sites of N-linked glycosylation (Asn 28 and Asn 63 ) to glutamine shows that the apoptogenic activity of glycodelin A is executed by the protein backbone. Glycosylation at Asn 28 appears to play a role in the extracellular secretion of the molecule, as mutation of Asn 28 resulted in a significant decrease in the amount of secreted protein, and loss of both glycosylation sites reduced the secretion drastically. Our results also suggest that the loss of glycosylation does not affect the dimerization status of the molecule.Glycodelin A (GdA), 1 also known as PP14 (placental protein-14), is a glycosylated dimeric 162-amino acid protein secreted by human endometrium in the late secretory phase of the menstrual cycle and in the early phase of pregnancy under the regulation of the hormone progesterone (1). Glycodelin is glycosylated at two of the three putative glycosylation sites (Asn 28 and Asn 63 ) (2). Observations of several research groups suggest that GdA is immunosuppressive in function (3), and previous studies from our laboratory indicate that this effect is due to its capacity to induce apoptosis in T cells (4). Interestingly, glycodelin S (GdS), another isoform of glycodelin synthesized by the seminal vesicles and accumulating in the seminal plasma, is not apoptogenic (26) even though both isoforms share the same amino acid sequence. As the glycans on both isoforms are different and as glycosylation has been demonstrated to play an important role in the contraceptive activity of GdA (13), it appeared logical to investigate the relevance of glycosylation to the apoptogenic function. However, attempts to deglycosylate GdA and GdS under native conditions using enzymes were not successful. Therefore, we resorted to molecular biology approaches to mutate the glycosylation sites and to express the protein in a eukaryotic system. The functional analysis of protein thus expressed proves that the apoptogenic activity of the molecule resides in its protein backbone, with the oligosaccharides being either permissive or non-permissive in the manifestation of this observed property. Furthermore, we have demonstrated that glycosylation at Asn 28 plays a role in the secretory rate of the protein, as the mutagenesis of the same drastically reduces protein secretion. We also have evidence to suggest that lack of glycosylation does not compromise the dimerization state of the molecule. EXPERIMENTAL PROCEDURESCells and Cell Lines-Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from healthy volunteers (male and female, 25-49 years old) using HISTOPAQUE-1077 (Sigma) accor...

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Glycodelins as regulators of early events of reproduction

Cited by 31 publications

References 28 publications

Angiogenic role for glycodelin in tumorigenesis

Angiogenic role for glycodelin in tumorigenesis

Glycodelin in reproductive endocrinology and hormone-related cancer

Analysis of the Role of Oligosaccharides in the Apoptotic Activity of Glycodelin A

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