Cytokines in Vertebrate Reproduction

Mechanisms determining survival and growth of the semi-allogeneic fetus in the maternal uterus are still not completely defined. Studies in mammals have shown that soluble substances with autocrine/paracrine action (cytokines) have a central role in modulating the maternal immune response and contributing to the expansion of fetal tissues in the maternal uterus. We hypothesized studies on different classes of vertebrates could help clarify the role of cytokines in acceptance of the embryo by the maternal tissues. We examined the presence of the cytokine interleukin-1 beta (IL-1β) and of its functional membrane receptor IL-1 receptor type I (IL-1R tI) in uterine/oviductal tissues of species with different reproductive strategies. In particular, we carried out studies on non-mammalian vertebrates (squamate reptiles, amphibians and elasmobranch fishes), presenting placental or aplacental viviparity, oviparity or ovuliparity. Since in ovuliparity eggs are released and fertilized in the external environment, species adopting this reproductive strategy can be considered a natural negative control in studies on materno-fetal immunotolerance. Findings showed The IL-1 system is expressed in the reproductive tissues of all the species regardless the vertebrate class or the reproductive strategy adopted. However, marked differences exist between ovuliparous species and oviparous and viviparous ones. In fact, expression of IL-1β and IL-1R tI is limited to the luminal epithelium in the ovuliparous species, while it is extended to most cellular components of the uterine wall (including connective tissue, glandular and endothelial cells, and the muscle layer) in oviparous and viviparous specimens. These findings highlight the role of the IL-1 system in the acquisition of the ability to retain the embryo in the female genital tract during the transition from ovuliparity to viviparity and suggest non-mammalian vertebrates as a good animal model for studies on cytokines in materno-fetal immunotolerance.