Secretory Endometrium Synthesizes Placental Protein 14*

Julkunen, Mervi; Koistinen, Riitta; Sjöberg, Jari; Rutanen, Eeva‐Marja; Wahlström, Torsten; Seppälä, Markku

doi:10.1210/endo-118-5-1782

Cited by 192 publications

(96 citation statements)

References 16 publications

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“…A retrospective study 15 divided 712 women who became pregnant after receiving donat-inhibiting the immune response of the endometrium to the embryo [25][26][27][28][29] . More specifically, it has been shown to primarily inhibit mixed lymphocyte reaction and natural killer cell activity 27,29 .…”

Section: Obesitymentioning

confidence: 99%

The Pathophysiology of Miscarriage in Women with Polycystic Ovary Syndrome. Review and Proposed Hypothesis of Mechanisms Involved

Essah¹,

Cheang²,

Nestler³

2004

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Section: Obesitymentioning

confidence: 99%

The Pathophysiology of Miscarriage in Women with Polycystic Ovary Syndrome. Review and Proposed Hypothesis of Mechanisms Involved

Essah¹,

Cheang²,

Nestler³

2004

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“…Thus, the amniotic fluid form of the glycoprotein that was shown to inhibit sperm-zona pellucida binding has been designated glycodelin-A (GdA). 1 During the menstrual cycle, GdA is not expressed in the proliferative endometrium, but increases significantly from the 4th post-ovulatory day, peaking around the 12th day (14). Thus, GdA is expressed at a minimum during the peri-ovulatory period of the cycle.…”

mentioning

confidence: 98%

Gender-specific Glycosylation of Human Glycodelin Affects Its Contraceptive Activity

Morris

Dell

Easton

et al. 1996

Journal of Biological Chemistry

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142

136

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We have recently demonstrated that a human amniotic fluid-derived glycoprotein, glycodelin-A (GdA; previously known as PP14 or PAEP), potently inhibits gamete binding in an established sperm-egg binding system and expresses immunosuppressive activities directed against a variety of different immune cell types. GdA has high mannose-, hybrid-, and complex-type biantennary oligosaccharides including structures with fucosylated or sialylated N,N-diacetyllactosediamine (GalNAc␤1-4GlcNAc) sequences, which are rare in other human glycoproteins. We now report the characterization of glycodelin-S (GdS). This is a human seminal plasma glycoprotein that is immunologically indistinguishable from GdA, but unlike the latter, does not inhibit human sperm-zona pellucida binding under hemizona assay conditions. Analysis of the N-glycans of GdS by mass spectrometry revealed that all glycoforms of GdS are different from those of GdA. GdS glycans are unusually fucose-rich, and the major complex-type structures are biantennary glycans with Lewis x (Gal␤1-4(Fuc␣1-3)GlcNAc) and Lewis y (Fuc␣1-2Gal␤1-4 (Fuc␣1-3)GlcNAc) antennae. It is probable that these highly fucosylated epitopes contribute to the immunosuppressive activity of human seminal plasma and to the low immunogenicity of sperm. This study provides the first evidence for gender-specific glycosylation that may serve to regulate key processes involved in human reproduction.

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“…Placental protein 14 (PP14) 1 or glycodelin A belongs to the family of hydrophobic molecule transporter proteins known as lipocalins. PP14, a 162-amino acid glycosylated protein, is secreted by the late secretory phase endometrium during the menstrual cycle (1) and has been proposed as a biochemical marker of endometrial function in women (2).…”

mentioning

confidence: 99%

Placental Protein 14 Induces Apoptosis in T Cells but Not in Monocytes

Mukhopadhyay¹,

Sundereshan²,

Rao³

et al. 2001

Journal of Biological Chemistry

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Substantial evidence exists in literature to suggest that placental protein 14 (PP14) (recently renamed glycodelin A), exhibits immunosuppressive properties and is an indispensable macromolecule in the maternal system for the establishment, maintenance, and progression of pregnancy. Though there are several reports substantiating the above, the mechanism of its action at the molecular level has not been elucidated as yet. In this paper we provide data that suggest that amniotic fluid PP14 and recombinant PP14 expressed in Pichia pastoris induce apoptosis in human peripheral blood lymphocytes upon activation, independent of monocytes. That PP14 has a direct apoptotic action on T cells but not on monocytes was also demonstrated by utilizing human cell lines. PP14 was shown to induce apoptosis in the human T cell lines, Jurkat and MOLT-4 cells, but not in the human monocytic cell line, U937. Placental protein 14 (PP14)1 or glycodelin A belongs to the family of hydrophobic molecule transporter proteins known as lipocalins. PP14, a 162-amino acid glycosylated protein, is secreted by the late secretory phase endometrium during the menstrual cycle (1) and has been proposed as a biochemical marker of endometrial function in women (2). The gene encoding the protein consists of three putative progesterone/ corticosterone response elements (3). Consistent with this is the finding that PP14 concentrations in the endometrial tissue, as well as in circulation, are highest in the late luteal phase and lowest in the periovulatory phase of the menstrual cycle (4 -6) in concert with progesterone levels (7). During pregnancy, PP14 concentration rises, peaking at ϳ10 -12 weeks, being high during the first and second trimesters of pregnancy, and declining thereafter (8 -10).PP14 has been shown to inhibit sperm-zona interaction (11) and is associated with endometrial preparation for blastocyst implantation (12, 13). Apart from this, PP14 has been shown to have immunosuppressive properties in that it inhibits both phytohemagglutinin (14) and anti-CD3 antibody-induced lymphocyte proliferation (15). PP14 also inhibits Natural Killer cell activity (16). That the protein is essential for normal pregnancy progression has been established by the association of low levels of PP14 with habitual abortion (17, 18), unexplained infertility (19), and establishment of pregnancy in women during those cycles in which normal concentrations of PP14 were detected (20). Despite the growing literature on the multifunctional role of PP14, the mechanism of action of this protein has not been delineated at the molecular level. Our studies demonstrate that the immunosuppressive effect of PP14 is the result of induction of apoptosis in T cells. The protein also induced apoptosis in the human T cell lines Jurkat and MOLT-4 but not in the monocyte cell line U937. EXPERIMENTAL PROCEDURES Cells and Cell Lines-Peripheral blood mononuclear cells (PBMCs)were isolated using Histopaque (Sigma) from freshly drawn blood of normal healthy donors (male and female; age 25-...

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Secretory Endometrium Synthesizes Placental Protein 14*

Cited by 192 publications

References 16 publications

The Pathophysiology of Miscarriage in Women with Polycystic Ovary Syndrome. Review and Proposed Hypothesis of Mechanisms Involved

The Pathophysiology of Miscarriage in Women with Polycystic Ovary Syndrome. Review and Proposed Hypothesis of Mechanisms Involved

Gender-specific Glycosylation of Human Glycodelin Affects Its Contraceptive Activity

Placental Protein 14 Induces Apoptosis in T Cells but Not in Monocytes

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