The Role of Membrane Progesterone Receptor Associated Proteins in Gynecological and Reproductive Disorders, and Cancers: An Editor’s Historical Perspective

How can a fetus with half of the antigens from a paternal source not be immunologically rejected? There is evidence that not only does the state of pregnancy fail to preclude invasion of cellular immune cells into uterine tissue, but, in fact, by progesterone (P) blocking the biogenic comma after dopamine, and a lower case t for this: it should read dopamine. This allows a greater infiltration of leukocytes. This invasion seems to be needed to aid in the creation of thinwalled spiral arteries for nutrient exchange between mother and fetus. Related to the speed of the development of these spiral arteries, it is not likely that the main mechanism involves neovascularization, since this is a slow genomic process which would operate by activation of nuclear progesterone receptors (nPRs). Instead, remodeling of the already pre-existing thick-walled uterine arteries by autoimmune mechanisms is more likely. Could the fetal placental unit somehow preclude these cellular immune cells from invading the fetal placental unit? These cells do, in fact infiltrate the fetal placental microenvironment composed of 70% natural killer cells, 20% macrophages, and 10% cytotoxic T-cells. Evidence does exist that one of the main ways of preventing immune rejection of the fetus is by P activating rapid acting membrane (m) PRs to produce immunomodulatory proteins e.g., the progesterone induced blocking factor (PIBF) and the progesterone receptor membrane component-1 protein (PGRMC-1). PIBF, for example, eventually suppresses natural killer cell cytotoxicity by stabilizing perforin granules and granzymes. Understanding these mechanisms has led to a scientifically based treatment regimen to achieve a successful pregnancy.