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Problem: Throughout the reproductive cycle and into early pregnancy, the normal endometrium undergoes changes in a range of leukocytes, epithelia, stromal fibroblasts, and vascular structures caused by intersecting effects of hormone balance and embryo implantation. The direct investigation in humans of reproductive tract responses during normal and physiologically altered cycles is not practical or feasible. METHOD AND STUDY: The aim of this study was to define immunological and morphological changes through immunohistological and morphometric evaluation of the endometrium throughout the menstrual cycle and the decidua during early gestation in the rhesus monkey, a tractable experimental animal model., Results: A zone-dependent method for the immunohistological description of the rhesus uterine mucosa was established and showed that leukocyte infiltration, stromal cell decidualization, glandular and vascular responses were zone- and cell type-dependent, and changed throughout the cycle and early pregnancy. Morphological heterogeneity of uterine natural killer cells in the cycling endometrium and gestational decidua were consistent with the recent characterization of phenotypic subsets., Conclusions: These data establish a morphological platform upon which to further study the regulation of endometrial responses to the hormonal mileau of pregnancy, the control of local leukocyte populations, and the responses to threatened pregnancy, infection, and inflammation., (© 2012 John Wiley & Sons A/S.)

While there is broad agreement that interactions of the human maternal immune system with the tissues and cells of the implanting embryo are likely to be critical contributors to pregnancy success, there remains a dearth of information which directly confirms this expectation. Although animal models of reproductive function often provide opportunities for confirming such hypotheses, progress in this area has been sporadic due to limitations of traditional laboratory or agricultural animal models, such as rodents, sheep, pigs and cattle. Many of these limitations derive from divergent modes of implantation and placentation across mammalian species. Over the past decade there has been progress in the development of the nonhuman primate as a model in which to address questions of pregnancy success in the area of immunology. The purpose of this review is to compare available model species, summarize current knowledge and recent progress with an emphasis on experimental in vivo manipulations, and suggest areas available for additional study and growth.

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step of tryptophan degradation along the kynurenine pathway, and is hypothesized to limit tryptophan availability at embryo implantation and prevent maternal T cell activation at the maternal-fetal interface. To determine if nonhuman primates are suitable models for investigating the role of IDO during pregnancy, we defined the expression of IDO in the rhesus monkey and common marmoset with particular attention to the female reproductive tract and placenta. IDO mRNA was detected by RT-PCR in the rhesus monkey term placenta, lung, small intestine, spleen, lymph node and nonpregnant uterus, and also in the common marmoset placenta. Immunohistochemical analysis of rhesus monkey tissues localized IDO to glandular epithelium of nonpregnant endometrium and first trimester decidua, vessel endothelium of nonpregnant myometrium, first trimester decidua and term decidua, and villous vessel endothelium and syncytiotrophoblast of term placenta. Western blot analysis confirmed IDO in rhesus monkey term placenta. In the common marmoset, IDO was detected in glandular epithelium of the nonpregnant uterus and in the decidua at day 60 and day 128 of gestation. IDO activity was higher in rhesus monkey and common marmoset decidua and placentas than in other tissues. Confirmation of IDO expression in rhesus monkey and common marmoset uterine and placental tissues supports the hypothesis that this enzyme regulates immune activation at the maternal-fetal interface and demonstrates that nonhuman primates may provide models with distinct similarities to human placentation to study the role of IDO in maternal-fetal immune dialogue.

Subsets of mononuclear cells, specific pregnancy proteins (SP-1, SP-3, PAPP-A) in the normal pregnancy decidua (NPD) and spontaneous abortion decidua (SAD), and trophoblast were studied. Significant decrease of lymphocytes infiltration was found in SAD. CD8+ cells rather than CD4+ cells predominated in NPD. CD4+ cells levels were lower in NPD in comparison with SAD. CD4+ lymphocytes rather than CD8+ cells predominated in SAD. Macrophages population was found to be increased in SAD in comparison with NPD. In blood vessels walls, cytoplasm of mononuclear cells and decidua stroma, PAPP-A and SP-3 were expressed in NPD and unexpressed or negative in SAD. In syncytiotrophoblast, SP-1 was expressed in normal pregnancy and unexpressed in spontaneous abortion. It is suggested that inadequate fetal-placental tissues counts of suppressor decidual lymphocytes, specific pregnancy proteins might be a cause of early spontaneous abortion.

Problem: There is increasing evidence that decidual lymphocytes play a major role in local interactions at the fetomaternal interface., Method: In this paper we use two-color flow cytometry to delineate the phenotype of lymphocytes obtained from human early decidua by mechanical dispersal technique., Results: The most abundant decidual lymphocytes expressed CD7, CD38, CD56, and CD2 markers, relatively small proportions of CD3+, CD8+, CD4+, CD16+, CD45RA+, CD11b+, and Leu8+ cells were also present. The vast majority of decidual CD7+ lymphocytes expressed CD38, CD2, and CD56 markers and were CD3-, CD8-, CD16-, and CD57-. Decidual CD3+ lymphocytes were weakly staining for TCR alpha/beta, lacked T-cell receptor (TCR) gamma/delta molecules, and approximately 40% of them expressed HLA-DR. All decidual CD8+ lymphocytes were CD2+ and the majority of them expressed CD38, CD56, and CD7 markers and were CD3- at the same time CD8+CD7- lymphocytes were found in decidua. According to the expression of the CD45RA marker, decidual CD8+ lymphocytes could be divided into two subsets: CD8+CD45RA+CD56+ and CD8+CD45RA-., Conclusions: These data clearly demonstrate that decidual lymphocytes display phenotypical features different from those of their counterparts in peripheral blood.