Embryo–Placento–Maternal Interaction and Biomarkers: From Diagnosis to Therapy – A Workshop Report

Than, Nándor Gábor; Paidas, Michael J.; Mizutani, Shigehiko; Sharma, Surendra; Padbury, Jamés F.; Barnea, Eytan R.

doi:10.1016/j.placenta.2007.01.017

Cited by 17 publications

(11 citation statements)

References 19 publications

(19 reference statements)

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“…Embryo implantation into maternal endometrium and placental formation with trophoblast invasion require a complex interplay of embryo-derived cell signaling for establishing maternal immune receptivity 1,2. This interplay was variously described over time by in vivo and in vitro models, and appears to involve initial polarization of the blastocyst, followed by cytokine signaling by IL-6, VEGF, and EGF among others 3–6.…”

Section: Introductionmentioning

confidence: 99%

Preimplantation factor promotes first trimester trophoblast invasion

Duzyj

Barnea

et al. 2010

American Journal of Obstetrics and Gynecology

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Objectives-Preimplantation factor (PIF) is a novel embryo-derived peptide which influences key processes in early pregnancy implantation, including immunity, adhesion, remodeling and apoptosis. Herein, we explore the effects of synthetic PIF (sPIF) on trophoblast invasion.Methods-Invasion patterns of immortalized cultured HTR-8 trophoblast cells were analyzed through Matrigel extracellular matrix +/− sPIF (25-100nM) in a transwell assay. Effects were compared with epidermal growth factor (EGF) 10μg/mL, scrambled aminoacid sequence of PIF, or media alone as controls.Results-sPIF enhances trophoblast invasion at physiologic doses [at 50nM 260% (174-346% 95% CI, p=0.05); 100nM 178% (170-184%, p<0.02)], compared to scrambled amnioacid sequence PIF or control media. EGF added to sPIF does not further enhance trophoblast invasion [sPIF 50nM +EGF,[238][239] p<0.03); sPIF 100nM+EGF 269% (265-273%, p<0.04)].Conclusion-PIF should be further investigated as it shows a potential preventative or therapeutic role for pregnancy complications associated with inadequate trophoblast invasion.

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Section: Introductionmentioning

confidence: 99%

Preimplantation factor promotes first trimester trophoblast invasion

Duzyj

Barnea

et al. 2010

American Journal of Obstetrics and Gynecology

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“…A similar activity has been traced in the blood in the form of placental exosomes. 66 A suppressive role can be exerted by embryo-associated suppressor factors, such as pre-implantation factor (PIF), as described by Barnea, 67 as well as by the well-described regeneration and tolerance factor (RTF) cytokine of Beaman and Hoversland, 68 whose neutralisation by a monoclonal antibody clearly induces abortion.…”

Section: Mechanisms Involved In the Acceptance Of Foeto-placental Unitmentioning

confidence: 99%

“…Seminal fluid is required as are the cells in the ejaculate. Therefore, 'tolerance' is prepared before implantation, 122 also possibly via embryo signals such as PIF 67 and follicular fluid G-CSF .…”

Section: New Partners?mentioning

confidence: 99%

REVIEW ARTICLE: Tolerance to the Foetal Allograft?

Chaouat¹,

Petitbarat

Dubanchet

et al. 2010

American J Rep Immunol

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“…In the context of recurrent pregnancy loss (RPL) PIF has two demonstrated beneficial effects: acting as a rescue factor to negate patients' embryo-toxic serum thereby preventing embryo demise and reducing systemic NK cells cytoxicity [7,12]. We reported that PIF is present in maternal circulation, and is expressed by the human placenta and fetus [4,5,[13][14][15]. Relevant to PIF's immune regulatory features, translational aspects to treatment of non-pregnant autoimmune and transplantation models were documented [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Preimplantation factor (*PIF) detection in maternal circulation in early pregnancy correlates with live birth (Bovine model)

Barnea¹,

Sivakumar²,

Stamatkin³

et al. 2014

Journal of Reproductive Immunology

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Background: Early identification of viable pregnancy is paramount for successful reproduction. Detection of specific signals from pre-implantation viable embryos in normal pregnancy circulation would indicate initiation of embryomaternal interaction and create a continuum to accurately reflect embryo/fetal well-being post-implantation. Viable mammalian embryos secrete PreImplantation Factor (PIF), a biomarker which plays key, multi-targeted roles to promote implantation, trophoblast invasion and modulate maternal innate and adaptive immunity toward acceptance. Anti-PIF monoclonal antibody (mAb-based chemiluminescent ELISA) accurately detects PIF in singly cultured embryos media and its increased levels correlate with embryo development up to the blastocyst stage. Herein reported that PIF levels (ELISA) in early maternal serum correlate with pregnancy outcome. Methods: Artificially inseminated (AI) blind-coded Angus cattle (N = 21-23) serum samples (day10,15 & 20 post-AI) with known calf birth were blindly tested, using both non-pregnant heifers (N = 30) and steer serum as negative controls. Assay properties and anti-PIF monoclonal antibody specificity were determined by examining linearity, spike and recovery experiments and testing the antibody against 234 different circulating proteins by microarray. Endogenous PIF was detected using <3 kDa filter separation followed by anti-PIF mAb-based affinity chromatography and confirmed by ELISA and HPLC. PIF expression was established in placenta using anti-PIF mAb-based IHC. Results: PIF detects viable pregnancy at day 10 post-AI with 91.3% sensitivity, reaching 100% by day 20 and correlating with live calf birth. All non-pregnant samples were PIF negative. PIF level in pregnant samples was a stringent 3 + SD higher as compared to heifers and steer sera. Assay is linear and spike and recovery data demonstrates lack of serum interference. Anti-PIF mAb is specific and does not interact with circulating proteins. Anti-PIF based affinity purification demonstrates that endogenous PIF is what ELISA detects. The early bovine placenta expresses PIF in the trophoblast layer. Conclusion: Data herein documents that PIF is a specific, reliable embryo-derived biomarker conveniently detectable in early maternal circulation. PIF ELISA emerges as practical tool to detect viable early pregnancy from day 20 post-AI.

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Embryo–Placento–Maternal Interaction and Biomarkers: From Diagnosis to Therapy – A Workshop Report

Cited by 17 publications

References 19 publications

Preimplantation factor promotes first trimester trophoblast invasion

Preimplantation factor promotes first trimester trophoblast invasion

REVIEW ARTICLE: Tolerance to the Foetal Allograft?

Preimplantation factor (*PIF) detection in maternal circulation in early pregnancy correlates with live birth (Bovine model)

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