Preimplantation antagonism of adrenomedullin action compromises fetoplacental development and reduces litter size.

Concentrations of adrenomedullin (ADM) in circulation, the uterus, and corpora lutea (CL) increase during pregnancy. We previously reported a temporal-spatial pattern of ADM level and gene expression of Adm and its receptor components, from early pregnancy through midpregnancy to late pregnancy in rats. Two earlier reports using an in vivo model of ADM antagonism demonstrated the important roles of ADM in the post-implantation period. Treatment with ADM receptor blocker hADM22-52 starting from gestation Day 8 or Day 14 resulted in fetal-placental growth restriction and reduction in litter size. In this study, the endogenous ADM actions were abolished in the preimplantation period by infusing the antagonist for the ADM receptor (hADM22-52) with the osmotic (Alzet) pump from Days 1-4 of pregnancy. We inferred that ADM, acting through the ADM receptor, had critical roles during preimplantation, as brief inhibition of ADM action by hADM22-52 during this period reduced litter size by restricting placental growth and increasing fetal resorption in midpregnancy.