Changes in Immune Response during Pig Gestation with a Focus on Cytokines.

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20-45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types. However, other non-immune cells, such as trophoblast cells, are important in immune pregnancy regulation. Numerous studies have shed light on the crucial roles of several cytokines that regulate the inflammatory processes that characterize the interface between the fetus and the mother throughout normal porcine gestation, but most of these reports are limited to the implantational and peri-implantational periods. Increase in some proinflammatory cytokines have been found in other gestational periods, such as placental remodeling. Porcine immune changes during delivery have not been studied as deeply as in other species. This review details some of the immune system cells actively involved in the fetomaternal interface during porcine gestation, as well as the principal cells, cytokines, and molecules, such as antibodies, that play crucial roles in sow pregnancy, both in early and mid-to-late gestation.

IFN-γ and IL-10: seric and placental profile during pig gestation Seric and placental cytokines in pig gestation.

Concentration of interferon-gamma and interleukin-10 in maternal serum and in maternal and fetal porcine placental extracts from different gestation periods was determined. Crossbred pigs' placental samples of 17, 30, 60, 70, and 114 days gestation and non-pregnant uteri were used. Interferon-gamma concentration was increased at the placental interface at 17 days, in maternal and fetal placenta, and decreased significantly in the remaining gestation periods. Interferon-gamma showed a peak in serum at 60 days. Regarding interleukin-10, placental tissue concentrations were unaltered, there were no significant differences with non-gestating uteri samples. In serum interleukin-10 increased at 17, 60, and 114 days gestation. At 17 days there are uterus structural and molecular changes that allow the embryos implantation and placenta development. The presence of interferon-gamma found at this moment in the interface would favor that placental growth. Moreover, its significant increase in serum at 60 days, would generate a proinflammatory cytokine pattern that facility the placental remodeling characteristic of this moment of porcine gestation. On the other hand, a significant interleukin-10 increase in serum at 17, 60 and 114 days could indicate its immunoregulatory role at a systemic level during pig gestation.

Integrins and ligands, are correlated at pig placental interface during pregnancy?

In the present work, we emphasize the studies about integrins and their receptors in pig placental interface at different times of gestation. Uterine placental interface (n=24) of 17-, 30-, 60- and 70-days gestation (dg) and non-pregnant uterus (n=4) of crossbred sows were used. The presence of αvß3 and α5ß1 integrins, and their ligands fibronectin (FN), and osteopontin (OPN) were detected by immunohistochemistry, and the immunolabelled area percentage (IAP) and the optical density (OD) were determined. The integrins and its ligands analyzed have presented peaks of expression in early and mid-gestation, both in IAP and the OD area decreasing at 70 dg. These temporal changes showed us that the molecules studied in this work participate in embryo/feto-maternal attachment, variably. Besides, we found a significant correlation both in the intensity and in the extension of immunostaining for trophoblastic FN and endometrial αvß3, and trophoblastic OPN and endometrial α5ß1, throughout the entire pig pregnancy. At late gestation, take place a notable placental remodelation with subsequent removal or renewal of folds at the uterine-placental interface that results in the loss of focal adhesions. The decrease of the expression of some integrins and their ligands in late gestation, particularly at 70 dg, would demonstrate that there would be other adhesion molecules and other ligands that could be participating in the establishment of the maternal-fetal interface.

IL-1ß, IL-2 and IL-4 concentration during porcine gestation.

In pigs, given the type of epitheliochorial and non-invasive placenta, the trophoblast is in intimate contact with maternal tissues. The dialogue established between the conceptus and the endometrium involves, among others, the immune system, which minimizes the chances of rejection of the embryo and promotes the establishment of pregnancy. The aim of this work was to determine the concentration of IL-1ß, IL-2 and IL-4 in sera and in extracts of maternal and fetal placenta from sows of different gestational periods. Reproductive tracts from 23 crossbreed sows, between 30 and 114 days of gestation (dg), and from 8 non-pregnant sows were used. The concentration of the cytokines was determined by ELISA. IL-1ß, IL-2 and IL-4 demonstrated a similar pattern of concentration at the placental interface and serum; they were found elevated in tissues at 30 and 60-70 dg, and significantly decreased at term, period in which the cytokines were significantly increased in serum. These results show that IL-1ß, IL-2, and IL-4 are differentially modulated during pregnancy and at term, and suggest an important role of these cytokines in defining the proinflammatory stage of these periods.