Novel Methods of Improving Fecundity and Various Pathological Disorders Based on a Hypothetical Model of Embryo Implantation

Abstract

Progesterone (P) is very involved in achieving successful embryo implantation. It aids in the creation of thinwalled spiral arteries which are needed for nutrient exchange between mother and fetus, by creating a cellular immune response, which removes the thick-cell walls of some of the uterine arteries thus creating spiral arteries. This uterine artery remodeling requires 5 days, but the embryo reaches the uterine cavity by day 3. Thus, P inhibits implantation at that time by stimulating a glycoprotein called mucin-1, which lines the uterine cavity and prevents the embryo from attaching until the mucin-1 barrier is finally breeched, on day 5. Progesterone also inhibits dopamine, which normally serves to decrease cellular permeability. Thus, by blocking dopamine, irritants infuse into the uterine tissue leading to an inflammatory response (70% natural killer cells). These natural killer cells would attack the fetal semi-allograft. However, P again serves to inhibit immune rejection of the fetal semi-allograft, by inducing cells of the fetal-placental unit to make a unique immune modulatory protein called the progesterone induced blocking factor (PIBF), which suppresses cellular immunity. This hypothetical model explains the beneficial effect of creating a greater inflammatory response by endometrial irritation (endometrial scratch), to improve number of spiral arteries, which may be deficient. In addition, this model explains the potential beneficial effect of luteal and first trimester supplementation of P, in improving fecundity and also the possibility of sympathomimetic amines releasing dopamine to similarly improve fecundity by diminishing excessive cellular permeability. Excessive cellular permeability may be the cause of various chronic medical conditions, since they seem to respond very well to dextroamphetamine treatment. Cancer cells also use the PIBF mechanism to escape immune surveillance. Thus, it is no surprise that P receptor antagonists can improve quality and length of life to patients with a variety of cancers.