This is particularly the case related to potential systemic effects of conceptus IFN-τ produced by domestic ruminants, and for potential uterine, and non-luteal effects of primate

CG. In this review, we will focus only on those initial conceptus signals (IFN-τ and CG) that Fer-1 molecular weight are thought responsible for CL rescue and limit our focus to the contribution of ruminant models to understanding the systemic effects of these conceptus signals on circulating immune cell function in primates. Readers desiring information regarding the effects of pregnancy on changes in populations of peripheral or endometrial resident immune cells are directed to recent reviews on this subject in primates,3 ruminants,12 swine13 and horses.14 In addition, there is an excellent recent review on the role of progesterone in altering immune responses during pregnancy.15 Human pregnancy recognition is characterized by production of CG from syncytiotrophoblast cells, beginning approximately Idasanutlin research buy 8–10 days after fertilization.3,16 CG is a member of the glycoprotein hormone family that includes LH, follicle

stimulating hormone and thyroid stimulating hormone.17 CG arose from a gene duplication event from the LH-β subunit roughly 34–50 million years ago; more than 80 million years after the first appearance of eutherian (i.e., true placental) mammals.18 CG binds to the LH/CG receptor and sustains the CL and progesterone (P4) production until sufficient P4 is produced by the placenta; the highest concentrations of human CG detected in maternal circulation occur during the first trimester of pregnancy. As in other species, humans exhibit significant immunomodulatory adaptations to pregnancy and the changing

hormonal milieu is likely a key driving force to these STK38 changes in the maternal immune system.19 Forty years after Medawar’s postulates on maternal acceptance of the semiallogeneic conceptus via immunomodulatory mechanisms, Wegmann et al.20 proposed that the immune system shifts to an antibody-based response (Th2) instead of a cell-mediated response (Th1) during pregnancy. The Th1 cytokine profile is associated with greater concentrations of interferon γ (IFN-γ), interleukin-2 (IL-2) and tumor necrosis factor-β (TNF-β). The Th2 cytokine profile is typified by increased levels of IL-4, IL-5, IL-6, IL-10, and IL-13.21,22 There appears to be a delicate balance between Th1 and Th2, with each cytokine profile regulating the other. Disruption of the Th1/Th2 balance has been implicated in miscarriages in a number of species.24 The Th2 cytokine profile can block the activation of Th1 cells, while Th1 cytokines inhibit Th2-cell proliferation.