Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction.

Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor-controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy-associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the foetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tracts, in trophoblast cells from normal and pre-eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer cells as possible targets.

Characterization of CD25-positive T cells during syngeneic pregnancy: production of stimulatory class II MHC molecules.

Various studies demonstrate that immunosuppression vis-à-vis paternal alloantigens may play a role for successful pregnancy. However, if this theory is true, the question that remains unanswered is how do syngeneic pregnancies manage to produce viable embryos. In allogeneic murine pregnancies immunosuppression is mediated by regulatory CD25(+)/Foxp3/CTLA-4 T cells. In order to evaluate whether these cells also play a role in syngeneic pregnancies, CD25(+)CD4(+) and CD25(+)CD8(+) were isolated from spleens of pregnant mice and examined as to the expression of specific suppressive and stimulatory markers, cytokine and soluble MHC class II antigen production. Interestingly, the CD25(+) cells and their products displayed an MHC-restricted stimulatory activity on total spleen cell proliferation assays. Although the CD25(+)CD4(+) and CD25(+)CD8(+) cells expressed Foxp3, they lacked CTLA-4, while expressing CD28. Non-specific proliferative effect was shown to be mediated by IL-3 and IL-4. The MHC-restricted proliferative effect; however, could be attributed to IA(d) molecules, which were detected in all culture supernatants of the T cell subpopulations tested and their elimination ablated the observed stimulatory activity. The detection of Ea, Eb1, Eb2 in addition to the Aa and Ab transcripts in these cells indicated the possible involvement of other class II gene combinations in this type of regulation. The results indicate that in the absence of paternal MHC alloantigens, maternal CD25(+) cells are involved in the development of immunostimulation to ensure foetal survival.