ABSTRACT
A large proportion of unexplained recurrent spontaneous abortions may be due to immunological causes. A predominantly Th1 response or defective production of Th2-type cytokines appear to predispose in spontaneous miscarriage. Dysregulation of the expression and/or of the activity of MMP-9 and MMP-2 has been observed in spontaneous early pregnancy failure. Preferential expression of Th1 proinflammatory cytokines is required in early pregnancy and at the end of pregnancy, Th2 anti-inflammatory cytokines are required in mid-pregnancy. The disruption of one or more of the mechanisms leading to tolerance in normal pregnancy may lead to miscarriage. Maternal genes may regulate the response to stress; luteal phase support and paternally inherited trophoblastic antigens may determine the cytokine balance in pregnancy. The exact mechanism by which decidual NK cells exert their immunomodulatory role in pregnancy is not fully understood. Several specific mechanisms have been suggested to contribute to fetal tolerance, and disturbances of these mechanisms may lead to pregnancy loss.
