The comparative approach in biological sciences has provided valuable insights into the role of different organ systems in adaptation and evolution, and seeks to establish unifying themes. This approach also plays a key role in identifying model species and systems for the study of specific questions and problems. Further, by applying the concept of homology, information about nonmammalian species may be used either to directly understand mammalian/human regulatory processes, or to formulate hypotheses for direct testing. Individual physiological systems function in a milieu provided by the integrated activities of all of the systems to adapt, adjust and sustain the organism in its environment. The overlapping interfaces between the different physiological systems provide fertile ground for new insights and to enhance our knowledge. These interdisciplinary areas are of great importance if we are to understand the full complexity of organismal function. Of particular interest are the interactions between the reproductive system and the immune system. The reproductive system is unique in that its primary role is to assure the continuity of the species, while the immune system provides internal protection and thus facilitates continued health and survival. The modus operandi of these 2 morphologically diffuse systems involves widely distributed chemical signals in response to environmental input, and both systems must interact for the normal functioning of each. While the major focus of reproductive-immune research has historically been with mammals, and has provided substantial insight into the interactions between these physiological systems, comparative studies offer unique perspectives. Further, dysregulation of normal physiological interactions between the reproductive and immune systems can lead to disorders and diseases effecting one system or the other. Thus, comparative studies of these interactions may shed some light upon the evolutionary mechanisms involved in such cases.

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Background Cellular treatments for repairing diseased tissues represent a promising clinical strategy. Umbilical cord tissue-derived cells (UTC) are a unique source of cells with a low immunogenic profile and potential for tissue repair. By using UTC from miniature swine, we previously demonstrated that despite their low immunogenic phenotype, UTC could induce an immune response under certain inflammatory conditions and after multiple subcutaneous (SC) injections. Given that repeat dosing of cells may be necessary to achieve a lasting therapeutic benefit, in this study, we examined approaches to avoid an immune response to multiple SC injections of UTC. Methods By using in vitro and in vivo measures of sensitization to SC cellular injections, we assessed the effects of varying the location of administration site, prolongation of timing between injections, and use of immunosuppressive treatments on repeated cellular injections in Massachusetts General Hospital major histocompatibility complex-defined miniature swine. Results Although under normal conditions, a single SC injection of major histocompatibility complex-mismatched UTC did not induce a detectable immune response, multiple SC injections of UTC demonstrated rapid humoral and cell-mediated immune responses. Avoidance of an immune response to repeat SC injection was achieved by concurrent immunosuppression with each dose of UTC. Conclusions UTC and other similar cell types believed to be nonimmunogenic have the potential to induce immune responses under certain conditions. These studies provide important considerations and guidelines for preclinical studies investigating allogeneic cellular therapies.

In elasmobranchs, a unique association exists between an immune tissue, the epigonal organ (EO), and the gonads. In this study, the histological and vascular relationships of the EO and ovarian follicles of the little skate, Leucoraja erinacea, were assessed. Perfusions of Evans blue dye and Batson's monomer showed a shared vascular pathway from the gonadal artery into the epigonal-ovary complex, with blood first entering the EO and then perfusing the ovarian follicles. Histological studies demonstrated direct cellular contact between epigonal leukocytes and the follicle wall (FW), as well as the presence of leukocytes between the steroidogenic theca and granulosa cells. In vitro analyses demonstrated that epigonal cells co-cultured with FW cells cause a dose-dependent inhibition of estrogen (E2) and testosterone (T) production. In contrast, conditioned media from epigonal leukocytes, stimulated or unstimulated with lipopolysaccharide (10 microg/ml), increase the production of E2 and T from FW cells of the ovaries. These studies provide a basis for further investigations of leukocyte secreted factors and cell contact modulation of follicular steroid production.

The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate ligand C-X-C motif chemokine ligand 12 (CXCL12) plays a critical role in regulating hematopoietic stem cell activation and subsequent cellular mobilization. Extensive studies of these genes have been conducted in mammals, but much less is known about the expression and function of CXCR4 and CXCL12 in non-mammalian vertebrates. In the present study, we identify simultaneous expression of CXCR4 and CXCL12 orthologs in the epigonal organ (the primary hematopoietic tissue) of the little skate, Leucoraja erinacea. Genetic and phylogenetic analyses were functionally supported by significant mobilization of leukocytes following administration of Plerixafor, a CXCR4 antagonist and clinically important drug. Our results provide evidence that, as in humans, Plerixafor disrupts CXCR4/CXCL12 binding in the little skate, facilitating release of leukocytes into the bloodstream. Our study illustrates the value of the little skate as a model organism, particularly in studies of hematopoiesis and potentially for preclinical research on hematological and vascular disorders.