Placental protein 14 levels in uterine flushing and plasma of women with unexplained infertility

Mackenna, Antonio; Li, Tin‐Chiu; Dalton, Caroline; Bolton, A.E.; Cooke, I. D.

doi:10.1016/s0015-0282(16)55803-8

Cited by 56 publications

(23 citation statements)

References 18 publications

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“…Similar data were reported for glycodelin, the main secretory product of luteal phase endometrial epithelium and one of the markers of a receptive endometrium. Its concentration in serum and uterine fluid increase in ovulatory cycles [16,17] and decrease in uterine fluid of infertile women, with no difference in serum levels in those patients [18,19]. Indeed, most proposed endometrial receptivity markers are not specific to the uterus, and thus it would be difficult to determine whether their serum concentrations play a role in predicting successful implantation.…”

Section: Blood and Uterine Fluid Biomarkersmentioning

confidence: 99%

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Aghajanova¹,

Hamilton²,

Giudice³

2008

Seminars in Cell & Developmental Biology

140

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Embryonic implantation is a dynamic process of paracrine interactions between the maternal compartment and the conceptus and involves a receptive endometrium and a developmentally competent blastocyst. Herein, we review histology, clinical approaches, and the promise of transcriptomics in elucidating mechanisms underlying implantation and development of biomarkers of uterine receptivity -with an eye to diagnose and treat implantation-based disorders of miscarriage, fetal growth restriction, pre-eclampsia, and infertility.Keywords human implantation; endometrium; microarray; blastocyst Challenges and approaches in studying the process of human implantation Clinical implicationsSuccessful embryo implantation is a crucial event in natural and assisted human reproduction. Blastocyst implantation is a dynamic process, involving embryo apposition, attachment to the maternal endometrial epithelium, and invasion into the endometrial stroma [1]. With in vitro fertilization (IVF), implantation failure can occur due to several factors [2], including embryonic defects such as chromosomal abnormalities, which are the most common cause of implantation failure [3,4]. Another widely acknowledged barrier to successful blastocyst implantation and, therefore, successful treatment of infertile women with implantation failure, is an inappropriately developed endometrium. It is well established that embryos cannot implant in a poorly matured endometrium [5], and this may be responsible for low implantation rates with transfer of "good quality" embryos. The success of embryonic implantation further relies upon cross-talk between the embryo and a receptive endometrium [5]. Optimization of IVF results are important for many reasons, and achieving optimal implantation is even more important in the setting of single embryo transfer, a common practice aimed to avoid multiple pregnancies.Corresponding author: Linda C. Giudice, MD, PhD, MSc, Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, The Robert B. Jaffe, MD Endowed Professor in the Reproductive Sciences, University of California, San Francisco, 505 Parnassus Ave., M1496, Box 0132, San Francisco, CA 94143-0132, Tel: +1 4154762564, Fax: +1 415476181, giudice@obgyn.ucsf.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The implantation window and challenges of studying it NIH Public AccessThe endometrium is receptive to blastocyst implantation during a spatially and temporally restricted "window", when the luminal epithelium is favorable for blastocyst implantation even in the absence of an implanting ...

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Section: Blood and Uterine Fluid Biomarkersmentioning

confidence: 99%

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Aghajanova¹,

Hamilton²,

Giudice³

2008

Seminars in Cell & Developmental Biology

140

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“…In such conditions, subnormal glycodelin concentrations have been reported in endometrium, uterine flushings and serum at the time of expected endometrial receptivity (82)(83)(84)(85). Both glycodelin mRNA and protein are downregulated in human first trimester miscarriage (86), and pregnant women with polycystic ovary syndrome (PCOS), who subsequently miscarry show subnormal rise of glycodelin serum concentration during the first trimester, compatible with weaker placentation (87).…”

Section: Conditions Related To Implantation and Placentation Failurementioning

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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“…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.…”

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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Placental protein 14 levels in uterine flushing and plasma of women with unexplained infertility

Cited by 56 publications

References 18 publications

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Glycodelin in reproductive endocrinology and hormone-related cancer

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

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