Since Medawar (1953), much attention has been given to the immunological paradox of the survival and growth of the semi-allogeneic fetus in the maternal uterus. Numerous studies, mainly on the human placenta, have established fundamental mechanisms of this phenomenon; however, many aspects are still unclear and the complex process has yet to be completely defined. One of the accepted principles is that the secretion and action of mediators, i.e. cytokines, at the materno-fetal interface have a central role. Focusing on the cytokine Interleukin-1 (IL-1) the review highlights the importance of a physiological approach based on evolutionary studies in animals using similar or different reproductive strategies. Data on IL-1 in viviparity and oviparity, two reproductive strategies in which female reproductive tissues have to deal with paternal-derived antigens on sperm, fertilized eggs, and embryo, will be presented and discussed in the light of materno-fetal immuntolerance. Ovuliparity, a reproductive modality in which the eggs are released from the female reproductive tract and fertilization and embryonic development take place in the external environment will also be extensively reported as a negative control in the studies on materno-fetal immunotolerance. The evidence shown reveals that non-mammalian vertebrates with different reproductive strategies represent a good model to understand biological mechanisms allowing fetal acceptance and growth in the maternal tissues.
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