Human Reproduction, Vol. 8, No. 7, pp. 1032-1038, 1993
© 1993 European Society of Human Reproduction and Embryology
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Embryonic resistance to tumour necrosis factor-
mediated cytotoxicity: novel mechanism underlying maternal immunological tolerance to the fetal allograft
1Institut de Médecine de la Reproduction de Montréal, Université de Montréal Montréal, Québec, Canada 2Centre de recherche de l'Hôpital Maisonneuve-Rosemont (HMR), Département d'Obstétrique-Gynécologie, HMR, and Université de Montréal Montréal, Québec, Canada
Correspondence: 3To whom correspondence should be addressed at: Clinique de fertilité, Hôpital Notre-Dame, 1560, rue Sherbrooke Est, Montréal (Québec), Canada H2L 4M1
The cytokine tumour necrosis factor-
(TNF) has been postulated to play an essential role in the cytotoxic activity of cell-mediated immunity against allogenic or tumour cells invading the host. Several tumour cell lines, however, are resistant to TNF mediated cytotoxicity and respond paradoxically by cellular proliferation and by autocrine secretion of TNF. In view of the metastatic character of the mammalian embryo, the aim of this study was to assess the potential of murine embryos to secrete TNF in vitro, to express TNF receptors and to resist TNF mediated cytotoxicity during their in-vitro development to the blastocyst stage. The potential of human embryos to secrete TNF in vitro until the blastocyst stage was also investigated. From a total of 11 human embryos, which were allowed to proceed to blastocyst formation, seven secreted TNF in the range of 2–117 pg/ml/24 h. A total of 123 C57BL/6J mouse embryos were studied of which 55% secreted TNF in the range of 1.25–3.95 mg/ml/24 h. The presence of high levels of exogenous TNF (10–300 IU) was not detrimental to the in-vitro development of murine embryos. Using immunohistochemical techniques, we were not able to detect the presence of type I or II TNF receptors on the surface of murine embryos. Our findings suggest that human and C57BL/6J murine embryos have the potential to secrete TNF in vitro during the developmental stages leading to blastocyst formation. In both species, the presence of TNF in the culture medium did not cause subsequent necrosis of the conceptus, suggesting that mammalian embryos may be TNF resistant cell lines. The observed embryonic resistance to TNF may be explained by the absence of TNF receptors by which the cytotoxic effect is usually mediated. It is suggested that embryonic resistance to physiological concentrations of TNF released by effectors of the host's immune system, could be via a mechanism underlying the maternal immunological tolerance to the fetal allograft.
Key words: embryo/immune system/in-vitro preimplantation development/TNF
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