Cytokine components and mucosal immunity in the oviduct of Xenopus laevis (amphibia, pipidae).

Most studies on the mucosal immunity in female reproductive tissues have been performed in mammals. In all species, apart from their reproductive strategies, immunity in the genital mucosa is required to defend the host against luminal pathogens. In this study we investigated the role of the innate immunity of the oviductal mucosa of Xenopus laevis, an amphibian characterized by external fertilization. In particular we examined the expression and localization of Interleukin-1ß (IL1B), Macrophage migration inhibitory factor (MIF) and Interleukin-1 receptor type 1 (IL1R1) in different oviductal portions including an upper glandular region, an intermediate and a lower aglandular region (the ovisac). Tissues were examined by immunohistochemistry and western blot using polyclonal antibodies against human molecules. IL1B, MIF and IL1R1 were all shown in the three oviductal regions examined, albeit with a general increase towards the external environment. A substantial difference among the cytokine components was also observed mainly in the epithelium of the glandular and intermediate regions. Specifically, all three molecules were expressed by the luminal ciliated cells while only IL1R1 was present in the unciliated cells at the bottom of the epithelial ingrowths. The expression of IL1R1 in these cells appeared as a continuous layer separating the epithelium from the underlying tissues. While supporting the role of the innate immune system for host's defense against pathogens, the peculiar distribution of the cytokine components in the oviduct of X. laevis suggests novel immunologic strategies useful to assure gland secretion essential for egg formation and fertilization.

Pro-inflammatory cytokines in animal and human gestation.

The story of cytokines in pregnancy began about 30 years ago, approximately in concomitance with the understanding that cytokines are autocrine-paracrine regulators of physiological processes. Pro-inflammatory cytokines are predominant in the early and late events of gestation, e.g. pregnancy establishment and parturition, both of which have been described as inflammatory-like events. Pro-inflammatory cytokines are also produced in response to microbes constantly in contact with the female reproductive tract. While a pro-inflammatory response is beneficial to successful pregnancy, an exaggerated response, as may occur for an unresolved infection, could result in an unfavorable pregnancy outcome in animals and humans. Therapeutic strategies are required to avoid the risks to the health of fetus and mother. In this review, we discuss the involvement of pro-inflammatory cytokines in pregnancy at implantation and parturition, including the pathologies which might be related to an alteration of the cytokine levels. We also deal with the use of anti-cytokines and/or anti-inflammatory mediators to antagonize the action of pro-inflammatory cytokines. Finally we discuss the potential of animal models to evaluate the association of cytokines in the establishment and maintenance of pregnancy.

Environmental levels of para-nonylphenol are able to affect cytokine secretion in human placenta.

BACKGROUND: para-Nonylphenol (p-NP) is a metabolite of alkylphenols widely used in the chemical industry and manufacturing. It accumulates in the environment, where it acts with estrogen-like activity. We previously showed that p-NP acts on human placenta by inducing trophoblast differentiation and apoptosis. OBJECTIVE: The aim of the present study was to investigate the effect of p-NP on cytokine secretion in human placenta. METHODS: In vitro cultures of chorionic villous explants from human placenta in the first trimester of pregnancy were treated with p-NP (10(13), 10(11), and 10(9) M) in 0.1% ethanol as vehicle. Culture medium was collected after 24 hr and assayed by specific immunoassays for the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: p-NP modulated cytokine secretion by inducing the release of GM-CSF, IFN-gamma, IL-1beta, IL-4, and IL-10, with a maximum effect at 10(11) M. It reduced the release of TNF-alpha at 10(13) M, whereas levels of IL-2 and IL-5 remained below the detection limit. IL-6 and IL-8 levels were 1001,000 times higher than those of other cytokines, and they were not affected by p-NP. We observed significant differences from controls (ethanol alone) only for GM-CSF and IL-10. CONCLUSION: An unbalanced cytokine network at the maternal--fetal interface may result in implantation failure, pregnancy loss, or other complications. The effects of extremely low doses of p-NP on the placental release of cytokines raise considerable concerns about maternal exposure to this endocrine disruptor during pregnancy.

Interleukin-1 in reproductive strategies.

Evolutionary studies on different classes of vertebrates could help clarify the role of cytokines in acceptance of the embryo by the maternal tissues. This review focuses on the cytokine interleukin-1 (IL-1) and reports on its presence in the female reproductive tract of species with different reproductive strategies, that is, viviparity, oviparity, and ovuliparity. Unlike oviparity and viviparity, ovuliparity does not involve any contact between paternal-derived fetal antigens and maternal tissues, because eggs are released unfertilized in the external environment. Therefore, we consider ovuliparity a natural negative control for mechanisms of materno-fetal immunotolerance. The goal of this review is to discuss 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.

Interleukin 1 in oviductal tissues of viviparous, oviparous, and ovuliparous species of amphibians.

In previous reports, we have shown that interleukin 1 (IL1), a cytokine associated with implantation in mice, is also expressed in reproductive tissues of viviparous squamate reptiles and cartilaginous fishes. In the present study, we investigated the expression of IL1B and its functional membrane receptor type I (IL1R1) in amphibians, a class of vertebrates that is characterized by different reproductive modes, including internal and external fertilization. In particular, we investigated the oviductal tissues of the aplacental viviparous Salamandra lanzai, the oviparous Triturus carnifex, and the ovuliparous Bufo bufo. In immunohistochemistry with anti-human IL1B and IL1R1 polyclonal antibodies we found that in S. lanzai, most cells in the uterine mucosa were immunoreactive for IL1B and IL1R1. In T. carnifex, IL1B and IL1R1 were present in ciliated luminal cells, and there was evidence of IL1B in glandular cells. In B. bufo, the expression of IL1B and IL1R1 was limited to the apical cytoplasm of the ciliated oviductal cells. Western blot analysis showed that a putative mature form of IL1B, similar to that seen in mammals, was present in the oviductal tissues of S. lanzai, whereas different forms, which probably correspond to an inactive pro-IL1B protein, were found in T. carnifex and B. bufo. A band that corresponded to the predicted 80-kDa human IL1R1 was found in S. lanzai and T. carnifex. Although the present study shows that IL1B and IL1R1 expression occurs in all reproductive modes, the differential expression patterns noted between ovuliparity and oviparity and viviparity may reflect the different roles of IL1 in the various reproductive modes.