Embryonic resistance to tumour necrosis factor-α mediated cytotoxicity: novel mechanism underlying maternal immunological tolerance to the fetal allograft

Lachapelle, Marie-Hélène; Miron, Pierre; Hemmings, Robert; Falcone, T.; Granger, Louis; Bourque, Jacques; Langlais, Jean

doi:10.1093/oxfordjournals.humrep.a138188

Cited by 33 publications

(12 citation statements)

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“…We have also determined the source of TNF-a mRNA to be the TGCs. The expression of TNF-a is consistent with previous reports (Hunt et al 1993;Lachapelle et al 1993); however, our data are the first to define the expression of TNF receptors in the early peri-implantation period. The expression of TNF-R1 by the embryo coincides with that of TNF-a, whereas by comparison TNF-R2 commenced on day 5.5 and only continued through to day 7.5.…”

Section: Discussionsupporting

confidence: 93%

Elevated concentration of TNF-? induces trophoblast differentiation in mouse blastocyst outgrowths

Whiteside

Boucaut

Teh

et al. 2003

Cell and Tissue Research

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Elevated expression of tumour necrosis factor-alpha (TNF-alpha) is associated with adverse pregnancy outcome. This study has examined the expression of TNF-alpha and its receptors (TNF-Rs) by mouse blastocysts and blastocyst outgrowths from day 4 to 9.5 of pregnancy and investigated the effects of elevated TNF-alpha on the inner cell mass (ICM) and trophoblast cells of blastocyst outgrowths. RT-PCR demonstrated TNF-alpha mRNA expression from day 7.5 to 9.5, TNF-R1 from day 6.5 to 9.5 and TNF-R2 from day 5.5 to 7.5 of pregnancy, and in situ hybridisation revealed the trophoblast giant cells (TGCs) of the early placenta as the site of TNF-alpha expression. Day 4 blastocysts were cultured in a physiologically high concentration of TNF-alpha (100 ng/ml) for 72 h to the outgrowth stage and then compared to blastocysts cultured in media alone. TNF-alpha-treated blastocyst outgrowths exhibited a significant reduction in ICM cells (mean +/- SD 23.90+/-10.42 vs 9.37+/-7.45, t-test, P<0.0001) with no significant change in the numbers of trophoblast cells (19.97+/-8.14 vs 21.73+/-7.79, t-test, P=0.39). Within the trophoblast cell population, the TNF-alpha-treated outgrowths exhibited a significant increase in multinucleated cells (14.10+/-5.53 vs 6.37+/-5.80, t-test, P<0.0001) and a corresponding significant decrease in mononucleated cells (5.87+/-3.60 vs 15.37+/-5.87, t-test, P<0.0001). In summary, this study describes the expression of TNF-alpha and its receptors during the peri-implantation period in the mouse. It also reports that elevated TNF-alpha restricts ICM proliferation in the blastocyst and changes the ratio of mononucleated to multinucleated trophoblast cells. These findings suggest a mechanism by which increased expression of TNF-alpha during trophoblast differentiation may be detrimental to pregnancy.

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Section: Discussionsupporting

confidence: 93%

Elevated concentration of TNF-? induces trophoblast differentiation in mouse blastocyst outgrowths

Whiteside

Boucaut

Teh

et al. 2003

Cell and Tissue Research

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“…Mouse pre-implantation embryos were found to express the TNFR1 (p60) form of the TNF receptor (Pampfer et al 1994b) and may secrete TNF under some circumstances (Lachapelle et al 1993). TNF exerts detrimental effects on pre-implantation embryo development.…”

Section: Tumour Necrosis Factor Alpha (Tnf)mentioning

confidence: 99%

Female Tract Cytokines and Developmental Programming in Embryos

Robertson

Chin

Schjenken

et al. 2015

Advances in Experimental Medicine and Biology

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In the physiological situation, cytokines are pivotal mediators of communication between the maternal tract and the embryo. Compelling evidence shows that cytokines emanating from the oviduct and uterus confer a sophisticated mechanism for 'fine-tuning' of embryo development, influencing a range of cellular events from cell survival and metabolism, through division and differentiation, and potentially exerting long-term impact through epigenetic remodelling. The balance between survival agents, including GM-CSF, CSF1, LIF, HB-EGF and IGFII, against apoptosis-inducing factors such as TNFα, TRAIL and IFNg, influence the course of preimplantation development, causing embryos to develop normally, adapt to varying maternal environments, or in some cases to arrest and undergo demise. Maternal cytokine-mediated pathways help mediate the biological effects of embryo programming, embryo plasticity and adaptation, and maternal tract quality control. Thus maternal cytokines exert influence not only on fertility and pregnancy progression but on the developmental trajectory and health of offspring. Defining a clear understanding of the biology of cytokine networks influencing the embryo is essential to support optimal outcomes in natural and assisted conception.

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“…The p75 and p55 TNF␣ receptors have, in fact, been shown to be absent in preimplantation murine embryos (Lachapelle et al, 1993). However, this explanation would require that the initial onset of functional responses to each of these mediators be coordinately and simultaneously regulated in endothelium.…”

Section: Endothelial Adhesion Molecules In Ontogenymentioning

confidence: 99%

E-selectin Expression and Stimulation by Inflammatory Mediators are Developmentally Regulated during Embryogenesis

Milstone

O’Donnell

Stavrakis

et al. 2000

Laboratory Investigation

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SUMMARY:Leukocyte recruitment during inflammation is specified, in part, by the spatial distribution and temporal regulation of endothelial adhesion molecules. In this study we investigated the developmental onset of E-selectin and intercellular adhesion molecule-1 (ICAM-1) basal expression and inducibility by inflammatory mediators as indices of lineage-restricted endothelial adhesion molecule expression. We studied both murine embryos and embryoid bodies (EB), derived from differentiated embryonic stem cells, to examine a broad range of endothelial ontogeny. Our results reveal that E-selectin and ICAM-1 are differentially regulated during development and that three stages define the ontogeny of the E-selectin-inducible response. The earliest endothelial lineage cells in Day 4 and Day 5 EB did not express E-selectin in the basal state or after stimulation. A second stage, observed between embryonic Day 9.5 (E9.5) and E11.5 to E12.5 in cultured embryo cells and transiently at Day 6 of EB differentiation, was characterized by basal expression that was not stimulated by inflammatory mediators. A third stage was characterized by both basal and inducible expression of E-selectin and was observed beginning at E12.5 to E13.5 in cultured embryo cells and at Day 7 in EB. In contrast ICAM-1 was stimulated at all of the embryonic stages examined and before the onset of E-selectin inducibility in both embryos and EB. E-selectin expression in embryos was also stimulated by introducing endotoxin into the embryonic, but not the maternal, peritoneum. This suggests that embryos are protected from inflammatory insults present in the maternal circulation. The developmentally regulated acquisition of E-selectin inducibility during embryogenesis likely involves changes in signal transduction cascades, transcription factors, and/or chromatin accessibility that specify inducible expression within the endothelial lineage and further restrict inducibility to particular endothelial subpopulations. (Lab Invest 2000, 80:943-954).

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Embryonic resistance to tumour necrosis factor-α mediated cytotoxicity: novel mechanism underlying maternal immunological tolerance to the fetal allograft

Cited by 33 publications

References 0 publications

Elevated concentration of TNF-? induces trophoblast differentiation in mouse blastocyst outgrowths

Elevated concentration of TNF-? induces trophoblast differentiation in mouse blastocyst outgrowths

Female Tract Cytokines and Developmental Programming in Embryos

E-selectin Expression and Stimulation by Inflammatory Mediators are Developmentally Regulated during Embryogenesis

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