Signaling between embryo and mother in early pregnancy: Basis for development of tolerance

Barnea, Eytan R.

doi:10.3109/9780203931677.002

Cited by 11 publications

(12 citation statements)

References 38 publications

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“…We reported that viable embryos secrete this novel peptide named, pre-implantation factor (PIF, 15 aa) [20][21][22][23][24][25] present in maternal circulation, expressed by the placenta. PIF plays a significant role in creating/maintaining maternal immune tolerance without suppression [22].…”

Section: Introductionmentioning

confidence: 99%

Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice

Weiss

Bernstein²,

Jones

et al. 2011

Endocrine

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Preimplantation factor (PIF) is a novel embryo-secreted immunomodulatory peptide. Its synthetic analog (sPIF) modulates maternal immunity without suppression. There is an urgent need to develop agents that could prevent the development of type 1 diabetes mellitus (TIDM). Herein, we examine sPIF's preventive effect on TIDM development by using acute adoptive-transfer (ATDM) and spontaneously developing (SDM) in non-obese diabetic (NOD) murine models. Diabetes was evaluated by urinary and plasma glucose, intraperitoneal glucose tolerance test (IPGTT), pancreatic islets insulin staining by immunohistochemistry and by pancreatic proteome evaluation using mass spectrometry, followed by signal pathway analysis. Continuous administration of sPIF for 4-weeks prevents diabetes development in ATDM model in >90% of recipients demonstrated by normal IPGTT, preserved islets architecture, number, and insulin staining. (P < 0.01). sPIF effect was specific; its protective effects are not replicated by scrambled PIF (χ(2) = 0.009) control. sPIF led also to increased circulating Th2 and Th1 cytokines. In SDM model, 4-week continuous sPIF administration prevented onset of diabetes for 21 weeks post-therapy (P < 0.01). Low-dose sPIF administration for 16 weeks prevented diabetes development up to 14 weeks post-therapy, evidenced by preserved islets architecture and insulin staining. In SDM model, pancreatic proteome pathway analysis demonstrated that sPIF regulates protein traffic, prevents protein misfolding and aggregation, and reduces oxidative stress and islets apoptosis, leading to preserved insulin staining. sPIF further increased insulin receptor expression and reduced actin and tubulin proteins, thereby blocking neutrophil invasion and inflammation. Exocrine pancreatic function was also preserved. sPIF administration results in marked prevention of spontaneous and induced adoptive-transfer diabetes suggesting its potential effectiveness in treating early-stage TIDM.

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Section: Introductionmentioning

confidence: 99%

Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice

Weiss

Bernstein²,

Jones

et al. 2011

Endocrine

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“…PIF can be seen in maternal circulation as soon as 4 days postembryo transfer indicating that it does come from the embryo. When PIF is seen in maternal plasma, the chance of normal pregnancy is significantly higher (103). PIF appears to have anti inflammatory effects.…”

Section: Endometrial Receptivitymentioning

confidence: 99%

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

et al. 2020

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Understanding what happens at the time of embryo implantation has been the subject of significant research. Investigators from many differing fields including maternal fetal medicine, microbiology, genetics, reproductive endocrinology and immunology have all been studying the moment the embryo interacts with the maternal endometrium. A perfect relationship between the uterus and the embryo, mediated by a tightly controlled interaction between the embryo and the endometrium, is required for successful implantation. Any factors affecting this communication, such as altered microbiome may lead to poor reproductive outcomes. Current theories suggest that altered microbiota may trigger an inflammatory response in the endometrium that affects the success of embryo implantation, as inflammatory mediators are tightly regulated during the adhesion of the blastocyst to the epithelial endometrial wall. In this review, we will highlight the various microbiome found during the periconceptual period, the microbiomes interaction with immunological responses surrounding the time of implantation, its effect on implantation, placentation and ultimately maternal and neonatal outcomes.

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“…This is an important observation as it is the first time that a clearly defined embryo‐derived compound has been found in very early pregnancy and in maternal peripheral circulation. Isolation and characterization of PIF from mouse embryo‐conditioned media have revealed it to be a novel 15–amino acid peptide 37–39 . (Barnea et al ., manuscript in preparation).…”

Section: Conceptmentioning

confidence: 99%

“…Isolation and characterization of PIF from mouse embryo-conditioned media have revealed it to be a novel 15-amino acid peptide. [37][38][39] (Barnea et al, manuscript in preparation).…”

Section: Pif: An Embryo-derived Peptide That Induces It and Prevents mentioning

confidence: 99%

Applying Embryo‐Derived Immune Tolerance to the Treatment of Immune Disorders

Barnea

2007

Annals of the New York Academy of Sciences

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Pregnancy is a unique immune state in which both mother and embryo/fetus tolerate and interact with one another through term, without interfering with the mother's native immunity. When the embryo is viable, it initiates maternal immune tolerance (IT)--ut not immune suppression. The balance is complex: some immune disorders are ameliorated during pregnancy, despite the presence of an "inflammatory" environment. We have identified a pregnancy viability biomarker--preimplantation factor (PIF)--secreted only by viable embryos, which helps to initiate this maternal tolerance and uterine receptivity. Using anti-PIF antibodies, we have detected PIF in the fetus and placenta. Beyond enhancing uterine receptivity locally, PIF has also been detected in maternal circulation, and may promote peripheral tolerance. In the fetus, PIF may help avoid a "graft-versus-host"-type reaction PIF exhibits unique potent immune-modulatory effects and its synthetic analogue has been shown to exert significant protection in diverse immune scenarios. Nontoxic, low-dose, short-term PIF administration has led to long-term effects in preclinical models of multiple sclerosis (MS), juvenile diabetes mellitus (JDM), and graft-versus-host disease (GVHD), in a manner enabling its translation into a clinical setting. Further investigation of this compound is warranted.

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Signaling between embryo and mother in early pregnancy: Basis for development of tolerance

Cited by 11 publications

References 38 publications

Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice

Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

Applying Embryo‐Derived Immune Tolerance to the Treatment of Immune Disorders

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